Scholars@Duke
Lorena Sue Beese

Lorena Sue Beese

James B. Duke Distinguished Professor of Biochemistry
Biochemistry
lorena.beese@duke.edu
Duke Box 3711, Durham, NC 27710
134 Nanaline H Duke, Durham, NC 27710

Selected Publications

Accurate Identification of Periplasmic Urea-binding Proteins by Structure- and Genome Context-assisted Functional Analysis.

Journal Article J Mol Biol · November 15, 2024 ABC transporters are ancient and ubiquitous nutrient transport systems in bacteria and play a central role in defining lifestyles. Periplasmic solute-binding proteins (SBPs) are components that deliver ligands to their translocation machinery. SBPs have di ... Full text Link to item Cite

Library Screening, In Vivo Confirmation, and Structural and Bioinformatic Analysis of Pentapeptide Sequences as Substrates for Protein Farnesyltransferase.

Journal Article Int J Mol Sci · May 13, 2024 Protein farnesylation is a post-translational modification where a 15-carbon farnesyl isoprenoid is appended to the C-terminal end of a protein by farnesyltransferase (FTase). This process often causes proteins to associate with the membrane and participat ... Full text Link to item Cite

Chromophore carbonyl twisting in fluorescent biosensors encodes direct readout of protein conformations with multicolor switching.

Journal Article Commun Chem · August 19, 2023 Fluorescent labeling of proteins is a powerful tool for probing structure-function relationships with many biosensing applications. Structure-based rules for systematically designing fluorescent biosensors require understanding ligand-mediated fluorescent ... Full text Link to item Cite

Thermally controlled intein splicing of engineered DNA polymerases provides a robust and generalizable solution for accurate and sensitive molecular diagnostics.

Journal Article Nucleic Acids Res · June 23, 2023 DNA polymerases are essential for nucleic acid synthesis, cloning, sequencing and molecular diagnostics technologies. Conditional intein splicing is a powerful tool for controlling enzyme reactions. We have engineered a thermal switch into thermostable DNA ... Full text Link to item Cite

Structure-Guided Discovery of Potent Antifungals that Prevent Ras Signaling by Inhibiting Protein Farnesyltransferase.

Journal Article J Med Chem · October 27, 2022 Infections by fungal pathogens are difficult to treat due to a paucity of antifungals and emerging resistances. Next-generation antifungals therefore are needed urgently. We have developed compounds that prevent farnesylation of Cryptoccoccus neoformans Ra ... Full text Link to item Cite

Cocrystal structure of an editing complex of klenow fragment with dna (3'-5' exonuclease dna polymerase protein-dna interaction x-ray crystallography/metal ion catalysis)

Chapter · January 1, 2020 High-resolution crystal structures of editing complexes of both duplex and single-stranded DNA bound to Escherichia coli DNA polymerase I large fragment (Klenow fragment) show four nucleotides of single-stranded DNA bound to the 3′ – 5′ exonuclease active ... Cite

Structure of DNA polymerase i Klenow fragment bound to duplex DNA

Chapter · January 1, 2020 Klenow fragment of Escherichia coli DNA polymerase I, which was cocrystallized with duplex DNA, positioned 11 base pairs of DNA in a groove that lies at right angles to the cleft that contains the polymerase active site and is adjacent to the 3' to 5' exon ... Full text Cite

Structural basis for the 3'- 5' exonuclease activity of escherichia coli dna polymerase i: A two metal ion mechanism

Chapter · January 1, 2020 The refined crystal structures of the large proteolytic fragment (Klenow fragment) of Escherichia coli DNA polymerase I and its complexes with a deoxynucleoside monophosphate product and a single-stranded DNA substrate offer a detailed picture of an editin ... Full text Cite

Using time-resolved crystallography and cryo-EM to investigate human DNA repair nucleases

Conference Acta Crystallographica Section A Foundations and Advances · July 20, 2019 Full text Cite

Sensing and Processing of DNA Interstrand Crosslinks by the Mismatch Repair Pathway.

Journal Article Cell Rep · October 31, 2017 DNA interstrand crosslinks (ICLs) that are repaired in non-dividing cells must be recognized independently of replication-associated DNA unwinding. Using cell-free extracts from Xenopus eggs that support neither replication nor transcription, we establish ... Full text Link to item Cite

Interplay of catalysis, fidelity, threading, and processivity in the exo- and endonucleolytic reactions of human exonuclease I.

Journal Article Proc Natl Acad Sci U S A · June 6, 2017 Human exonuclease 1 (hExo1) is a member of the RAD2/XPG structure-specific 5'-nuclease superfamily. Its dominant, processive 5'-3' exonuclease and secondary 5'-flap endonuclease activities participate in various DNA repair, recombination, and replication p ... Full text Link to item Cite

A Farnesyltransferase Acts to Inhibit Ectopic Neurite Formation in C. elegans.

Journal Article PLoS One · 2016 Genetic pathways that regulate nascent neurite formation play a critical role in neuronal morphogenesis. The core planar cell polarity components VANG-1/Van Gogh and PRKL-1/Prickle are involved in blocking inappropriate neurite formation in a subset of mot ... Full text Link to item Cite

The Closing Mechanism of DNA Polymerase I at Atomic Resolution.

Journal Article Structure · September 1, 2015 DNA polymerases must quickly and accurately distinguish between similar nucleic acids to form Watson-Crick base pairs and avoid DNA replication errors. Deoxynucleoside triphosphate (dNTP) binding to the DNA polymerase active site induces a large conformati ... Full text Link to item Cite

Rapid analysis of protein farnesyltransferase substrate specificity using peptide libraries and isoprenoid diphosphate analogues.

Journal Article ACS Chem Biol · August 15, 2014 Protein farnesytransferase (PFTase) catalyzes the farnesylation of proteins with a carboxy-terminal tetrapeptide sequence denoted as a Ca1a2X box. To explore the specificity of this enzyme, an important therapeutic target, solid-phase peptide synthesis in ... Full text Link to item Cite

Crystal structures of the fungal pathogen Aspergillus fumigatus protein farnesyltransferase complexed with substrates and inhibitors reveal features for antifungal drug design.

Journal Article Protein Sci · March 2014 Species of the fungal genus Aspergillus are significant human and agricultural pathogens that are often refractory to existing antifungal treatments. Protein farnesyltransferase (FTase), a critical enzyme in eukaryotes, is an attractive potential target fo ... Full text Link to item Cite

Visualization of synaptic inhibition with an optogenetic sensor developed by cell-free protein engineering automation.

Journal Article J Neurosci · October 9, 2013 We describe an engineered fluorescent optogenetic sensor, SuperClomeleon, that robustly detects inhibitory synaptic activity in single, cultured mouse neurons by reporting intracellular chloride changes produced by exogenous GABA or inhibitory synaptic act ... Full text Link to item Cite

Structural factors that determine selectivity of a high fidelity DNA polymerase for deoxy-, dideoxy-, and ribonucleotides.

Journal Article J Biol Chem · August 17, 2012 In addition to discriminating against base pair mismatches, DNA polymerases exhibit a high degree of selectivity for deoxyribonucleotides over ribo- or dideoxynucleotides. It has been proposed that a single active site residue (steric gate) blocks producti ... Full text Link to item Cite

Covalent protein-oligonucleotide conjugates by copper-free click reaction.

Journal Article Bioorg Med Chem · July 15, 2012 Covalent protein-oligodeoxynucleotide (protein-ODN) conjugates are useful in a number of biological applications, but synthesizing discrete conjugates-where the connection between the two components is at a defined location in both the protein and the ODN- ... Full text Link to item Cite

Structural evidence for the rare tautomer hypothesis of spontaneous mutagenesis.

Journal Article Proc Natl Acad Sci U S A · October 25, 2011 Even though high-fidelity polymerases copy DNA with remarkable accuracy, some base-pair mismatches are incorporated at low frequency, leading to spontaneous mutagenesis. Using high-resolution X-ray crystallographic analysis of a DNA polymerase that catalyz ... Full text Link to item Cite

Structures of Cryptococcus neoformans protein farnesyltransferase reveal strategies for developing inhibitors that target fungal pathogens.

Journal Article J Biol Chem · October 7, 2011 Cryptococcus neoformans is a fungal pathogen that causes life-threatening infections in immunocompromised individuals, including AIDS patients and transplant recipients. Few antifungals can treat C. neoformans infections, and drug resistance is increasing. ... Full text Link to item Cite

Purification, crystallization and preliminary X-ray diffraction analysis of the human mismatch repair protein MutSβ.

Journal Article Acta Crystallogr Sect F Struct Biol Cryst Commun · August 1, 2011 MutSβ is a eukaryotic mismatch repair protein that preferentially targets extrahelical unpaired nucleotides and shares partial functional redundancy with MutSα (MSH2-MSH6). Although mismatch recognition by MutSα has been shown to involve a conserved Phe-X- ... Full text Link to item Cite

The structure of a high fidelity DNA polymerase bound to a mismatched nucleotide reveals an "ajar" intermediate conformation in the nucleotide selection mechanism.

Journal Article J Biol Chem · June 3, 2011 To achieve accurate DNA synthesis, DNA polymerases must rapidly sample and discriminate against incorrect nucleotides. Here we report the crystal structure of a high fidelity DNA polymerase I bound to DNA primer-template caught in the act of binding a mism ... Full text Link to item Cite

Structures of human exonuclease 1 DNA complexes suggest a unified mechanism for nuclease family.

Journal Article Cell · April 15, 2011 Human exonuclease 1 (hExo1) plays important roles in DNA repair and recombination processes that maintain genomic integrity. It is a member of the 5' structure-specific nuclease family of exonucleases and endonucleases that includes FEN-1, XPG, and GEN1. W ... Full text Link to item Cite

Structural Biochemistry of CaaX Protein Prenyltransferases

Journal Article · January 1, 2011 Protein prenylation is a posttranslational lipid modification required for proper function by over 100 proteins in the eukaryotic cell. A family of structurally related protein prenyltransferase enzymes carry out this reaction: protein farnesyltransferase ... Full text Cite

Structure-based design and synthesis of potent, ethylenediamine-based, mammalian farnesyltransferase inhibitors as anticancer agents.

Journal Article J Med Chem · October 14, 2010 A potent class of anticancer, human farnesyltransferase (hFTase) inhibitors has been identified by "piggy-backing" on potent, antimalarial inhibitors of Plasmodium falciparum farnesyltransferase (PfFTase). On the basis of a 4-fold substituted ethylenediami ... Full text Open Access Link to item Cite

Structural mechanisms underlying DNA replication and human DNA mismatch repair

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · August 22, 2010 Link to item Cite

MutLalpha and proliferating cell nuclear antigen share binding sites on MutSbeta.

Journal Article J Biol Chem · April 9, 2010 MutSbeta (MSH2-MSH3) mediates repair of insertion-deletion heterologies but also triggers triplet repeat expansions that cause neurological diseases. Like other DNA metabolic activities, MutSbeta interacts with proliferating cell nuclear antigen (PCNA) via ... Full text Link to item Cite

The mechanism of the translocation step in DNA replication by DNA polymerase I: a computer simulation analysis.

Journal Article Structure · January 13, 2010 High-fidelity DNA polymerases copy DNA rapidly and accurately by adding correct deoxynucleotide triphosphates to a growing primer strand of DNA. Following nucleotide incorporation, a series of conformational changes translocate the DNA substrate by one bas ... Full text Link to item Cite

Structural analysis of semi-specific oligosaccharide recognition by a cellulose-binding protein of thermotoga maritima reveals adaptations for functional diversification of the oligopeptide periplasmic binding protein fold.

Journal Article J Biol Chem · November 27, 2009 Periplasmic binding proteins (PBPs) constitute a protein superfamily that binds a wide variety of ligands. In prokaryotes, PBPs function as receptors for ATP-binding cassette or tripartite ATP-independent transporters and chemotaxis systems. In many instan ... Full text Link to item Cite

Discrimination between right and wrong purine dNTPs by DNA polymerase I from Bacillus stearothermophilus.

Journal Article Biochemistry · June 2, 2009 We used a series of dATP and dGTP analogues to determine how DNA polymerase I from Bacillus stearothermophilus (BF), a prototypical A family polymerase, uses N-1, N(2), N-3, and N(6) of purine dNTPs to differentiate between right and wrong nucleotide incor ... Full text Link to item Cite

Structural adaptations that modulate monosaccharide, disaccharide, and trisaccharide specificities in periplasmic maltose-binding proteins.

Journal Article J Mol Biol · May 29, 2009 Periplasmic binding proteins comprise a superfamily that is present in archaea, prokaryotes, and eukaryotes. Periplasmic binding protein ligand-binding sites have diversified to bind a wide variety of ligands. Characterization of the structural mechanisms ... Full text Link to item Cite

Structural basis for binding and selectivity of antimalarial and anticancer ethylenediamine inhibitors to protein farnesyltransferase.

Journal Article Chem Biol · February 27, 2009 Protein farnesyltransferase (FTase) catalyzes an essential posttranslational lipid modification of more than 60 proteins involved in intracellular signal transduction networks. FTase inhibitors have emerged as a significant target for development of antica ... Full text Link to item Cite

Structural analysis of a periplasmic binding protein in the tripartite ATP-independent transporter family reveals a tetrameric assembly that may have a role in ligand transport.

Journal Article J Biol Chem · November 21, 2008 Several bacterial solute transport mechanisms involve members of the periplasmic binding protein (PBP) superfamily that bind and deliver ligand to integral membrane transport proteins in the ATP-binding cassette, tripartite tricarboxylate transporter, or t ... Full text Link to item Cite

Ligand-induced conformational changes in a thermophilic ribose-binding protein.

Journal Article BMC Struct Biol · November 19, 2008 BACKGROUND: Members of the periplasmic binding protein (PBP) superfamily are involved in transport and signaling processes in both prokaryotes and eukaryotes. Biological responses are typically mediated by ligand-induced conformational changes in which the ... Full text Link to item Cite

Structure of protein geranylgeranyltransferase-I from the human pathogen Candida albicans complexed with a lipid substrate.

Journal Article J Biol Chem · November 14, 2008 Protein geranylgeranyltransferase-I (GGTase-I) catalyzes the transfer of a 20-carbon isoprenoid lipid to the sulfur of a cysteine residue located near the C terminus of numerous cellular proteins, including members of the Rho superfamily of small GTPases a ... Full text Link to item Cite

Caged protein prenyltransferase substrates: tools for understanding protein prenylation.

Journal Article Chem Biol Drug Des · September 2008 Originally designed to block the prenylation of oncogenic Ras, inhibitors of protein farnesyltransferase currently in preclinical and clinical trials are showing efficacy in cancers with normal Ras. Blocking protein prenylation has also shown promise in th ... Full text Link to item Cite

The MutSalpha-proliferating cell nuclear antigen interaction in human DNA mismatch repair.

Journal Article J Biol Chem · May 9, 2008 We have examined the interaction parameters, conformation, and functional significance of the human MutSalpha(.) proliferating cell nuclear antigen (PCNA) complex in mismatch repair. The two proteins associate with a 1:1 stoichiometry and a K(D) of 0.7 mic ... Full text Link to item Cite

Dissecting the differences between the alpha and beta anomers of the oxidative DNA lesion FaPydG.

Journal Article Chemistry · 2008 The oxidative DNA lesion, FaPydG rapidly anomerizes to form a mixture of the alpha and beta anomer. To investigate the mutagenic potential of both forms, we prepared stabilized bioisosteric analogues of both configurational isomers and incorporated them in ... Full text Link to item Cite

Structure-based design of robust glucose biosensors using a Thermotoga maritima periplasmic glucose-binding protein.

Journal Article Protein Sci · October 2007 We report the design and engineering of a robust, reagentless fluorescent glucose biosensor based on the periplasmic glucose-binding protein obtained from Thermotoga maritima (tmGBP). The gene for this protein was cloned from genomic DNA and overexpressed ... Full text Link to item Cite

Structure of the human MutSalpha DNA lesion recognition complex.

Journal Article Mol Cell · May 25, 2007 Mismatch repair (MMR) ensures the fidelity of DNA replication, initiates the cellular response to certain classes of DNA damage, and has been implicated in the generation of immune diversity. Each of these functions depends on MutSalpha (MSH2*MSH6 heterodi ... Full text Link to item Cite

Chemical biology of mutagenic translesion DNA replicaton

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · March 25, 2007 Link to item Cite

Catalytically caged isoprenoid diphosphates for the study of protein prenylation

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · March 25, 2007 Link to item Cite

Resistance mutations at the lipid substrate binding site of Plasmodium falciparum protein farnesyltransferase.

Journal Article Mol Biochem Parasitol · March 2007 The post-translational farnesylation of proteins serves to anchor a subset of intracellular proteins to membranes in eukaryotic organisms and also promotes protein-protein interactions. This enzymatic reaction is carried out by protein farnesyltransferase ... Full text Link to item Cite

Following an environmental carcinogen N2-dG adduct through replication: elucidating blockage and bypass in a high-fidelity DNA polymerase.

Journal Article Nucleic Acids Res · 2007 We have investigated how a benzo[a]pyrene-derived N2-dG adduct, 10S(+)-trans-anti-[BP]-N2-dG ([BP]G*), is processed in a well-characterized Pol I family model replicative DNA polymerase, Bacillus fragment (BF). Experimental results are presented that revea ... Full text Link to item Cite

The structural basis for the mutagenicity of O(6)-methyl-guanine lesions.

Journal Article Proc Natl Acad Sci U S A · December 26, 2006 Methylating agents are widespread environmental carcinogens that generate a broad spectrum of DNA damage. Methylation at the guanine O(6) position confers the greatest mutagenic and carcinogenic potential. DNA polymerases insert cytosine and thymine with s ... Full text Link to item Cite

The crystal structure of a thermophilic glucose binding protein reveals adaptations that interconvert mono and di-saccharide binding sites.

Journal Article J Mol Biol · September 15, 2006 Periplasmic binding proteins (PBPs) comprise a protein superfamily that is involved in prokaryotic solute transport and chemotaxis. These proteins have been used to engineer reagentless biosensors to detect natural or non-natural ligands. There is consider ... Full text Link to item Cite

Conversion of protein farnesyltransferase to a geranylgeranyltransferase.

Journal Article Biochemistry · August 15, 2006 Posttranslational modifications are essential for the proper function of a number of proteins in the cell. One such modification, the covalent attachment of a single isoprenoid lipid (prenylation), is carried out by the CaaX prenyltransferases, protein far ... Full text Link to item Cite

Thematic review series: lipid posttranslational modifications. Structural biology of protein farnesyltransferase and geranylgeranyltransferase type I.

Journal Article J Lipid Res · April 2006 More than 100 proteins necessary for eukaryotic cell growth, differentiation, and morphology require posttranslational modification by the covalent attachment of an isoprenoid lipid (prenylation). Prenylated proteins include members of the Ras, Rab, and Rh ... Full text Link to item Cite

Observation of DNA replication past damaged DNA by X-ray crystallography.

Conference CHEMICAL RESEARCH IN TOXICOLOGY · December 1, 2005 Link to item Cite

Observation of DNA replication past damaged DNA by X-ray crystallography

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · August 28, 2005 Link to item Cite

Replication and repair of the oxidative DNA lesions 8-oxoG and FaPyG

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · March 13, 2005 Link to item Cite

Structure of a high fidelity DNA polymerase bound to a benzo[a]pyrene adduct that blocks replication.

Journal Article J Biol Chem · February 4, 2005 Of the carcinogens to which humans are most frequently exposed, the polycyclic aromatic hydrocarbon benzo[a]pyrene (BP) is one of the most ubiquitous. BP is a byproduct of grilled foods and tobacco and fuel combustion and has long been linked to various hu ... Full text Link to item Cite

Observing translesion synthesis of an aromatic amine DNA adduct by a high-fidelity DNA polymerase.

Journal Article J Biol Chem · November 26, 2004 Aromatic amines have been studied for more than a half-century as model carcinogens representing a class of chemicals that form bulky adducts to the C8 position of guanine in DNA. Among these guanine adducts, the N-(2'-deoxyguanosin-8-yl)-aminofluorene (G- ... Full text Link to item Cite

Crystallographic analysis of CaaX prenyltransferases complexed with substrates defines rules of protein substrate selectivity.

Journal Article J Mol Biol · October 15, 2004 Post-translational modifications are essential for the proper function of many proteins in the cell. The attachment of an isoprenoid lipid (a process termed prenylation) by protein farnesyltransferase (FTase) or geranylgeranyltransferase type I (GGTase-I) ... Full text Link to item Cite

Error-prone replication of oxidatively damaged DNA by a high-fidelity DNA polymerase.

Journal Article Nature · September 9, 2004 Aerobic respiration generates reactive oxygen species that can damage guanine residues and lead to the production of 8-oxoguanine (8oxoG), the major mutagenic oxidative lesion in the genome. Oxidative damage is implicated in ageing and cancer, and its prev ... Full text Link to item Cite

Structures of mismatch replication errors and observed in a DNA polymerase

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · August 22, 2004 Link to item Cite

Structural genomics of engineerable proteins

Conference PROTEIN SCIENCE · August 1, 2004 Link to item Cite

Crystallographic analysis reveals that anticancer clinical candidate L-778,123 inhibits protein farnesyltransferase and geranylgeranyltransferase-I by different binding modes.

Journal Article Biochemistry · July 20, 2004 Many signal transduction proteins that control growth, differentiation, and transformation, including Ras GTPase family members, require the covalent attachment of a lipid group by protein farnesyltransferase (FTase) or protein geranylgeranyltransferase ty ... Full text Link to item Cite

Crystal structures of the anticancer clinical candidates R115777 (Tipifarnib) and BMS-214662 complexed with protein farnesyltransferase suggest a mechanism of FTI selectivity.

Journal Article Biochemistry · June 8, 2004 The search for new cancer therapeutics has identified protein farnesyltransferase (FTase) as a promising drug target. This enzyme attaches isoprenoid lipids to signal transduction proteins involved in growth and differentiation. The two FTase inhibitors (F ... Full text Link to item Cite

Structures of mismatch replication errors observed in a DNA polymerase.

Journal Article Cell · March 19, 2004 Accurate DNA replication is essential for genomic stability. One mechanism by which high-fidelity DNA polymerases maintain replication accuracy involves stalling of the polymerase in response to covalent incorporation of mismatched base pairs, thereby favo ... Full text Link to item Cite

Structure of mammalian protein geranylgeranyltransferase type-I.

Journal Article EMBO J · November 17, 2003 Featured Publication Protein geranylgeranyltransferase type-I (GGTase-I), one of two CaaX prenyltransferases, is an essential enzyme in eukaryotes. GGTase-I catalyzes C-terminal lipidation of >100 proteins, including many GTP- binding regulatory proteins. We present the first ... Full text Link to item Cite

Dual protein farnesyltransferase-geranylgeranyltransferase-I inhibitors as potential cancer chemotherapeutic agents.

Journal Article J Med Chem · July 3, 2003 A series of novel diaryl ether lactams have been identified as very potent dual inhibitors of protein farnesyltransferase (FTase) and protein geranylgeranyltransferase I (GGTase-I), enzymes involved in the prenylation of Ras. The structure of the complex f ... Full text Link to item Cite

Processive DNA synthesis observed in a polymerase crystal suggests a mechanism for the prevention of frameshift mutations.

Journal Article Proc Natl Acad Sci U S A · April 1, 2003 Featured Publication DNA polymerases replicate DNA by adding nucleotides to a growing primer strand while avoiding frameshift and point mutations. Here we present a series of up to six successive replication events that were obtained by extension of a primed template directly ... Full text Link to item Cite

Reaction path of protein farnesyltransferase at atomic resolution.

Journal Article Nature · October 10, 2002 Featured Publication Protein farnesyltransferase (FTase) catalyses the attachment of a farnesyl lipid group to numerous essential signal transduction proteins, including members of the Ras superfamily. The farnesylation of Ras oncoproteins, which are associated with 30% of hum ... Full text Link to item Cite

3-Aminopyrrolidinone farnesyltransferase inhibitors: design of macrocyclic compounds with improved pharmacokinetics and excellent cell potency.

Journal Article J Med Chem · June 6, 2002 A series of macrocyclic 3-aminopyrrolidinone farnesyltransferase inhibitors (FTIs) has been synthesized. Compared with previously described linear 3-aminopyrrolidinone FTIs such as compound 1, macrocycles such as 49 combined improved pharmacokinetic proper ... Full text Link to item Cite

The crystal structure of human protein farnesyltransferase reveals the basis for inhibition by CaaX tetrapeptides and their mimetics.

Journal Article Proc Natl Acad Sci U S A · November 6, 2001 Featured Publication Protein farnesyltransferase (FTase) catalyzes the attachment of a farnesyl lipid group to the cysteine residue located in the C-terminal tetrapeptide of many essential signal transduction proteins, including members of the Ras superfamily. Farnesylation is ... Full text Link to item Cite

Synthesis and evaluation of novel pyrrolidinone-based farnesyltransferase inhibitors.

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · April 1, 2001 Link to item Cite

2 Structure of protein farnesyltransferase

Journal Article Enzymes · January 1, 2001 Full text Cite

Conversion of Tyr361 beta to Leu in mammalian protein farnesyltransferase impairs product release but not substrate recognition.

Journal Article Biochemistry · November 14, 2000 Protein farnesyltransferase catalyzes the lipid modification of protein substrates containing Met, Ser, Gln, or Ala at their C-terminus. A closely related enzyme, protein geranylgeranyltransferase type I, carries out a similar modification of protein subst ... Full text Link to item Cite

Crystal structure of a pol alpha family DNA polymerase from the hyperthermophilic archaeon Thermococcus sp. 9 degrees N-7.

Journal Article J Mol Biol · June 2, 2000 The 2.25 A resolution crystal structure of a pol alpha family (family B) DNA polymerase from the hyperthermophilic marine archaeon Thermococcus sp. 9 degrees N-7 (9 degrees N-7 pol) provides new insight into the mechanism of pol alpha family polymerases th ... Full text Link to item Cite

The basis for K-Ras4B binding specificity to protein farnesyltransferase revealed by 2 A resolution ternary complex structures.

Journal Article Structure · February 15, 2000 BACKGROUND: The protein farnesyltransferase (FTase) catalyzes addition of the hydrophobic farnesyl isoprenoid to a cysteine residue fourth from the C terminus of several protein acceptors that are essential for cellular signal transduction such as Ras and ... Full text Link to item Cite

Postpartum hemorrhage: a plan of attack.

Journal Article Nurs Spectr (Wash D C) · June 14, 1999 Link to item Cite

Crystal structure of farnesyl protein transferase complexed with a CaaX peptide and farnesyl diphosphate analogue.

Journal Article Biochemistry · November 24, 1998 The crystallographic structure of acetyl-Cys-Val-Ile-selenoMet-COOH and alpha-hydroxyfarnesylphosphonic acid (alphaHFP) complexed with rat farnesyl protein transferase (FPT) (space group P61, a = b = 174. 13 A, c = 69.71 A, alpha = beta = 90 degrees, gamma ... Full text Link to item Cite

Crystallization and preliminary diffraction analysis of a hyperthermostable DNA polymerase from a Thermococcus archaeon.

Journal Article Acta Crystallogr D Biol Crystallogr · September 1, 1998 The hyperthermostable DNA polymerase from a marine Thermococcus archaeon has been crystallized in space group P212121, with unit-cell dimensions a = 94.8, b = 98.2, c = 112.2 A with one molecule per asymmetric unit. Conditions for data collection at 98 K h ... Full text Link to item Cite

Cocrystal structure of protein farnesyltransferase complexed with a farnesyl diphosphate substrate.

Journal Article Biochemistry · July 7, 1998 Protein farnesyltransferase (FTase) catalyzes the transfer of the hydrophobic farnesyl group from farnesyl diphosphate (FPP) to cellular proteins such as Ras at a cysteine residue near their carboxy-terminus. This process is necessary for the subcellular l ... Full text Link to item Cite

Kinetic analysis of zinc ligand mutants of mammalian protein farnesyltransferase.

Journal Article Biochemistry · March 31, 1998 Protein farnesyltransferase (FTase) is a zinc metalloenzyme that catalyzes the prenylation of several proteins that are important in cellular regulatory events. A specific residue of FTase, Cys299 in the beta subunit previously identified as essential for ... Full text Link to item Cite

Visualizing DNA replication in a catalytically active Bacillus DNA polymerase crystal.

Journal Article Nature · January 15, 1998 Featured Publication DNA polymerases copy DNA templates with remarkably high fidelity, checking for correct base-pair formation both at nucleotide insertion and at subsequent DNA extension steps. Despite extensive biochemical, genetic and structural studies, the mechanism by w ... Full text Link to item Cite

Protein farnesyltransferase.

Journal Article Curr Opin Struct Biol · December 1997 In the past year, the crystal structure of alpha beta heterodimeric protein farnesyltransferase from rat was reported to a resolution of 2.25 A. Farnesyltransferase catalyzes the essential post-translational lipidation of Ras and several other cellular sig ... Full text Link to item Cite

Crystal structure of protein farnesyltransferase at 2.25 angstrom resolution.

Journal Article Science · March 21, 1997 Featured Publication Protein farnesyltransferase (FTase) catalyzes the carboxyl-terminal lipidation of Ras and several other cellular signal transduction proteins. The essential nature of this modification for proper function of these proteins has led to the emergence of FTase ... Full text Link to item Cite

Crystal structure of a thermostable Bacillus DNA polymerase I large fragment at 2.1 A resolution.

Journal Article Structure · January 15, 1997 BACKGROUND: The study of DNA polymerases in the Pol l family is central to the understanding of DNA replication and repair. DNA polymerases are used in many molecular biology techniques, including PCR, which require a thermostable polymerase. In order to l ... Full text Link to item Cite

Structures of nascent duplex DNA bound to a thermostable DNA polymerase at 1.9 Å resolution

Conference Acta Crystallographica Section A Foundations of Crystallography · August 8, 1996 Full text Cite

Crystallization and preliminary characterization of a hyperthermostable archeal DNA polymerase

Conference Acta Crystallographica Section A Foundations of Crystallography · August 8, 1996 Full text Cite

Crystal structures of the Klenow fragment of DNA polymerase I complexed with deoxynucleoside triphosphate and pyrophosphate.

Journal Article Biochemistry · December 28, 1993 Crystal structures of the Klenow fragment (KF) of DNA polymerase I from Escherichia coli complexed with deoxynucleoside triphosphate (dNTP) or with pyrophosphate (PPi) determined to 3.9-A resolution by X-ray crystallography show these molecules binding wit ... Full text Link to item Cite

Structure of DNA polymerase I Klenow fragment bound to duplex DNA.

Journal Article Science · April 16, 1993 Klenow fragment of Escherichia coli DNA polymerase I, which was cocrystallized with duplex DNA, positioned 11 base pairs of DNA in a groove that lies at right angles to the cleft that contains the polymerase active site and is adjacent to the 3' to 5' exon ... Full text Link to item Cite

Structural basis for the 3'-5' exonuclease activity of Escherichia coli DNA polymerase I: a two metal ion mechanism.

Journal Article EMBO J · January 1991 The refined crystal structures of the large proteolytic fragment (Klenow fragment) of Escherichia coli DNA polymerase I and its complexes with a deoxynucleoside monophosphate product and a single-stranded DNA substrate offer a detailed picture of an editin ... Full text Link to item Cite

Correction for specimen movement after acquisition of element-specific electron microprobe images.

Journal Article J Microsc · November 1989 Because a long time is generally required to generate X-ray maps of specific elements by electron beam methods, images are subject to a loss of resolution due to stage movement. Methods have been previously described for correcting stage drift during expos ... Full text Link to item Cite

Cocrystal structure of an editing complex of Klenow fragment with DNA.

Journal Article Proc Natl Acad Sci U S A · December 1988 High-resolution crystal structures of editing complexes of both duplex and single-stranded DNA bound to Escherichia coli DNA polymerase I large fragment (Klenow fragment) show four nucleotides of single-stranded DNA bound to the 3'-5' exonuclease active si ... Full text Link to item Cite

Genetic and crystallographic studies of the 3',5'-exonucleolytic site of DNA polymerase I.

Journal Article Science · April 8, 1988 Site-directed mutagenesis of the large fragment of DNA polymerase I (Klenow fragment) yielded two mutant proteins lacking 3',5'-exonuclease activity but having normal polymerase activity. Crystallographic analysis of the mutant proteins showed that neither ... Full text Link to item Cite

Structure of microtubules with reduced hydration. Comparison of results from X-ray diffraction and electron microscopy.

Journal Article J Mol Biol · August 5, 1987 A recent model for the structure of microtubules is used to interpret X-ray fiber diffraction patterns from microtubules, obtained under various conditions. The results suggest that tubulin may undergo conformational changes under conditions of reduced wat ... Full text Link to item Cite

Microtubule structure at 18 A resolution.

Journal Article J Mol Biol · March 20, 1987 A model for the structure of microtubules at a resolution of 18 A (1 A = 0.1 nm) is described, based on X-ray fiber diffraction data from hydrated reassembled calf brain microtubules. The model was derived by an iterative solvent flattening refinement proc ... Full text Link to item Cite

Contact x-ray microscopy. A new technique for imaging cellular fine structure.

Journal Article Biophys J · January 1986 Contact x-ray microscopy potentially allows living, wet cells to be visualized at a resolution of up to 100 A. Furthermore, differential absorption by specific elements permits the study of the distribution of those elements in biological specimens. In con ... Full text Link to item Cite

Carbohydrate metabolism disorders in kidney diseases

Journal Article Anales del Programa Academico de Medicina · 1969 Cite