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|1wms, resolution 1.25Å ()|
|Gene:||Rab9 (Homo sapiens)|
High resolution crystal structure of human Rab9 GTPase: a novel antiviral drug target
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.
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
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.