High resolution crystal structure of human Rab9 GTPase: a novel antiviral drug target
[RAB9A_HUMAN] Involved in the transport of proteins between the endosomes and the trans Golgi network.
Publication Abstract from PubMed
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.