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

The Journal of Biological Chemistry
Michael A Hast, L S Beese

Abstract

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 and other essential signal transduction proteins. In humans, GGTase-I and the homologous protein farnesyltransferase (FTase) are targets of anticancer therapeutics because of the role small GTPases play in oncogenesis. Protein prenyltransferases are also essential for many fungal and protozoan pathogens that infect humans, and have therefore become important targets for treating infectious diseases. Candida albicans, a causative agent of systemic fungal infections in immunocompromised individuals, is one pathogen for which protein prenylation is essential for survival. Here we present the crystal structure of GGTase-I from C. albicans (CaGGTase-I) in complex with its cognate lipid substrate, geranylgeranylpyrophosphate. This structure provides a high-resolution picture of a non-mammalian protein prenyltransferase. There are significant variations between species in critical areas of the active site, including the isoprenoid-binding pocket, as well as the putative product exit g...Continue Reading

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Citations

Nov 28, 2013·PloS One·David FournierMiguel A Andrade-Navarro
Sep 3, 2019·Acta Crystallographica. Section F, Structural Biology Communications·Zhenzhen YangWeidong Liu
Aug 24, 2019·Frontiers in Microbiology·Floris Schoeters, Patrick Van Dijck
May 28, 2019·Virulence·Ana Camila Oliveira SouzaJarrod R Fortwendel
Dec 23, 2019·RSC Medicinal Chemistry·Pimyupa ManaswiyoungkulPatrick T Gunning
Jun 24, 2020·ACS Chemical Biology·Sang Hu KimLeah E Cowen

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