1wms | pdb_00001wms
High resolution crystal structure of human Rab9 GTPase: a novel antiviral drug target
|
Overview
Rab GTPases and their effectors facilitate vesicular transport by, tethering donor vesicles to their respective target membranes. Rab9, mediates late endosome to trans-Golgi transport and has recently been, found to be a key cellular component for human immunodeficiency virus-1, Ebola, Marburg, and measles virus replication, suggesting that it may be a, novel target in the development of broad spectrum antiviral drugs. As part, of our structure-based drug design program, we have determined the crystal, structure of a C-terminally truncated human Rab9 (residues 1-177) to, 1.25-A resolution. The overall structure shows a characteristic nucleotide, binding fold consisting of a six-stranded beta-sheet surrounded by five, alpha-helices with a tightly bound GDP molecule in the active site., Structure-based sequence alignment of Rab9 with other Rab proteins reveals, that its active site consists of residues highly conserved in the Rab, GTPase family, implying a common catalytic mechanism. However, Rab9, contains seven regions that are significantly different in conformation, from other Rab proteins. Some of those regions coincide with putative, effector-binding sites and switch I and switch II regions identified by, structure/sequence alignments. The Rab9 structure at near atomic, resolution provides an excellent model for structure-based antiviral drug, design.
About this Structure
1WMS is a Single protein structure of sequence from Homo sapiens with GDP as ligand. Full crystallographic information is available from OCA.
Reference
High resolution crystal structure of human Rab9 GTPase: a novel antiviral drug target., Chen L, DiGiammarino E, Zhou XE, Wang Y, Toh D, Hodge TW, Meehan EJ, J Biol Chem. 2004 Sep 17;279(38):40204-8. Epub 2004 Jul 19. PMID:15263003
Page seeded by OCA on Mon Nov 12 19:52:34 2007
