Alkyl and Aryl Transferases

• 

  Subject Areas on Research

  • 3-Aminopyrrolidinone farnesyltransferase inhibitors: design of macrocyclic compounds with improved pharmacokinetics and excellent cell potency. 
  • A novel protein geranylgeranyltransferase-I inhibitor with high potency, selectivity, and cellular activity. 
  • A phase II window trial of procarbazine and topotecan in children with high-grade glioma: a report from the children's oncology group. 
  • Aberrant dolichol chain lengths as biomarkers for retinitis pigmentosa caused by impaired dolichol biosynthesis. 
  • Absence of the CAAX endoprotease Rce1: effects on cell growth and transformation. 
  • COQ2 nephropathy: a newly described inherited mitochondriopathy with primary renal involvement. 
  • Caged protein prenyltransferase substrates: tools for understanding protein prenylation. 
  • Characterization of a zinc finger DNA-binding protein expressed specifically in Petunia petals and seedlings. 
  • Characterization of cis-regulatory regions responsible for developmental regulation of the gibberellin biosynthetic gene GA1 in Arabidopsis thaliana. 
  • Cocrystal structure of protein farnesyltransferase complexed with a farnesyl diphosphate substrate. 
  • Control of the innate immune response by the mevalonate pathway. 
  • Conversion of Tyr361 beta to Leu in mammalian protein farnesyltransferase impairs product release but not substrate recognition. 
  • Conversion of protein farnesyltransferase to a geranylgeranyltransferase. 
  • Crystal structure of farnesyl protein transferase complexed with a CaaX peptide and farnesyl diphosphate analogue. 
  • Crystal structure of protein farnesyltransferase at 2.25 angstrom resolution. 
  • Crystal structures of the anticancer clinical candidates R115777 (Tipifarnib) and BMS-214662 complexed with protein farnesyltransferase suggest a mechanism of FTI selectivity. 
  • Crystallographic analysis of CaaX prenyltransferases complexed with substrates defines rules of protein substrate selectivity. 
  • Crystallographic analysis reveals that anticancer clinical candidate L-778,123 inhibits protein farnesyltransferase and geranylgeranyltransferase-I by different binding modes. 
  • Della proteins and gibberellin-regulated seed germination and floral development in Arabidopsis. 
  • Developmental regulation of the gibberellin biosynthetic gene GA1 in Arabidopsis thaliana. 
  • Discovery of geranylgeranyltransferase-I inhibitors with novel scaffolds by the means of quantitative structure-activity relationship modeling, virtual screening, and experimental validation. 
  • Dual protein farnesyltransferase-geranylgeranyltransferase-I inhibitors as potential cancer chemotherapeutic agents. 
  • Effects of pharmacologic inhibition of protein geranylgeranyltransferase type I on aqueous humor outflow through the trabecular meshwork. 
  • Elevated DNA polymerase alpha, DNA polymerase beta, and DNA topoisomerase II in a melphalan-resistant rhabdomyosarcoma xenograft that is cross-resistant to nitrosoureas and topotecan. 
  • Enzymology and biology of CaaX protein prenylation. 
  • Evidence for a catalytic role of zinc in protein farnesyltransferase. Spectroscopy of Co2+-farnesyltransferase indicates metal coordination of the substrate thiolate. 
  • Expression of functional bacterial undecaprenyl pyrophosphate synthase in the yeast rer2{Delta} mutant and CHO cells. 
  • Extraintestinal dissemination of Salmonella by CD18-expressing phagocytes. 
  • Farnesylation of YDJ1p is required for function at elevated growth temperatures in Saccharomyces cerevisiae. 
  • Farnesylation of nonpeptidic thiol compounds by protein farnesyltransferase. 
  • Farnesyltransferase inhibitors alter the prenylation and growth-stimulating function of RhoB. 
  • GGTase-I deficiency reduces tumor formation and improves survival in mice with K-RAS-induced lung cancer. 
  • Genetic characterization and functional analysis of the GID1 gibberellin receptors in Arabidopsis. 
  • H-Ras peptide and protein substrates bind protein farnesyltransferase as an ionized thiolate. 
  • High affinity for farnesyltransferase and alternative prenylation contribute individually to K-Ras4B resistance to farnesyltransferase inhibitors. 
  • High level expression of mammalian protein farnesyltransferase in a baculovirus system. The purified protein contains zinc. 
  • Identification of a cysteine residue essential for activity of protein farnesyltransferase. Cys299 is exposed only upon removal of zinc from the enzyme. 
  • Influence of metal ions on substrate binding and catalytic activity of mammalian protein geranylgeranyltransferase type-I. 
  • Inhibition of purified p21ras farnesyl:protein transferase by Cys-AAX tetrapeptides. 
  • Intraarterial O6-benzylguanine enables the specific therapy of nitrosourea-resistant intracranial human glioma xenografts in athymic rats with 1,3-bis(2-chloroethyl)-1-nitrosourea. 
  • Isolation of protein prenyltransferases from bovine brain and baculovirus expression system. 
  • Kinetic analysis of zinc ligand mutants of mammalian protein farnesyltransferase. 
  • Kinetic studies of protein farnesyltransferase mutants establish active substrate conformation. 
  • Kinetics of protein farnesyltransferase: sigmoidal vs hyperbolic behavior as a function of assay conditions. 
  • Ligation of the alpha2M* signaling receptor regulates synthesis of cytosolic phospholipase A2. 
  • Long-Chain Polyprenols Promote Spore Wall Formation in Saccharomyces cerevisiae. 
  • Lysine(164)alpha of protein farnesyltransferase is important for both CaaX substrate binding and catalysis. 
  • Mammalian protein geranylgeranyltransferase. Subunit composition and metal requirements. 
  • Mechanisms of protein prenylation and role in G protein function. 
  • New fungal metabolite geranylgeranyltransferase inhibitors with antifungal activity. 
  • Non-peptidic, non-prenylic inhibitors of the prenyl protein-specific protease Rce1. 
  • Overexpression of AtCPS and AtKS in Arabidopsis confers increased ent-kaurene production but no increase in bioactive gibberellins. 
  • Phase I and pharmacokinetic study of lonafarnib, SCH 66336, using a 2-week on, 2-week off schedule in patients with advanced solid tumors. 
  • Phase II and pharmacodynamic study of the farnesyltransferase inhibitor R115777 as initial therapy in patients with metastatic pancreatic adenocarcinoma. 
  • Post-prenylation-processing enzymes as new targets in oncogenesis. 
  • Preclinical and clinical pharmacodynamic assessment of L-778,123, a dual inhibitor of farnesyl:protein transferase and geranylgeranyl:protein transferase type-I. 
  • Prenylated c17orf37 induces filopodia formation to promote cell migration and metastasis. 
  • Prenylation and G protein signaling. 
  • Properties and kinetic mechanism of recombinant mammalian protein geranylgeranyltransferase type I. 
  • Protein Geranylgeranyltransferase Type 1 as a Target in Cancer. 
  • Protein farnesyltransferase and geranylgeranyltransferase share a common alpha subunit. 
  • Protein farnesyltransferase in embryogenesis, adult homeostasis, and tumor development. 
  • Protein farnesyltransferase. 
  • Protein farnesyltransferase: kinetics of farnesyl pyrophosphate binding and product release. 
  • Protein prenylation: unique fats make their mark on biology. 
  • Protein prenyltransferases. 
  • Proteolysis-independent downregulation of DELLA repression in Arabidopsis by the gibberellin receptor GIBBERELLIN INSENSITIVE DWARF1. 
  • Rapid analysis of protein farnesyltransferase substrate specificity using peptide libraries and isoprenoid diphosphate analogues. 
  • Reaction path of protein farnesyltransferase at atomic resolution. 
  • Resistance mutations at the lipid substrate binding site of Plasmodium falciparum protein farnesyltransferase. 
  • Restricted substrate specificity for the geranylgeranyltransferase-I enzyme in Cryptococcus neoformans: implications for virulence. 
  • Role of farnesyltransferase in ABA regulation of guard cell anion channels and plant water loss. 
  • Structure of mammalian protein geranylgeranyltransferase type-I. 
  • Structure of protein geranylgeranyltransferase-I from the human pathogen Candida albicans complexed with a lipid substrate. 
  • Structures of Cryptococcus neoformans protein farnesyltransferase reveal strategies for developing inhibitors that target fungal pathogens. 
  • Substitution of cadmium for zinc in farnesyl:protein transferase alters its substrate specificity. 
  • Substrate binding is required for release of product from mammalian protein farnesyltransferase. 
  • Synthesis of isomeric 3-piperidinyl and 3-pyrrolidinyl benzo[5,6]cyclohepta[1,2-b]pyridines: sulfonamido derivatives as inhibitors of Ras prenylation. 
  • The Arabidopsis F-box protein SLEEPY1 targets gibberellin signaling repressors for gibberellin-induced degradation. 
  • The Arabidopsis GA1 locus encodes the cyclase ent-kaurene synthetase A of gibberellin biosynthesis. 
  • The Arabidopsis SLEEPY1 gene encodes a putative F-box subunit of an SCF E3 ubiquitin ligase. 
  • The GA2 locus of Arabidopsis thaliana encodes ent-kaurene synthase of gibberellin biosynthesis. 
  • The LS locus of pea encodes the gibberellin biosynthesis enzyme ent-kaurene synthase A. 
  • The RAM1 gene encoding a protein-farnesyltransferase beta-subunit homologue is essential in Cryptococcus neoformans. 
  • The basis for K-Ras4B binding specificity to protein farnesyltransferase revealed by 2 A resolution ternary complex structures. 
  • The crystal structure of human protein farnesyltransferase reveals the basis for inhibition by CaaX tetrapeptides and their mimetics. 
  • The farnesyl protein transferase inhibitor SCH66336 is a potent inhibitor of MDR1 product P-glycoprotein. 
  • The synergistic combination of the farnesyl transferase inhibitor lonafarnib and paclitaxel enhances tubulin acetylation and requires a functional tubulin deacetylase. 
  • Thematic review series: lipid posttranslational modifications. Structural biology of protein farnesyltransferase and geranylgeranyltransferase type I. 
  • cDNA cloning and expression of rat and human protein geranylgeranyltransferase type-I.