1WMS

High resolution crystal structure of human Rab9 GTPase: a novel antiviral drug target

Summary for 1WMS

• Entry DOI: 10.2210/pdb1wms/pdb
• Descriptor: Ras-related protein Rab-9A, GUANOSINE-5'-DIPHOSPHATE (3 entities in total)
• Functional Keywords: gtpase, protein transport
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane; Lipid-anchor; Cytoplasmic side (Potential): P51151
• Total number of polymer chains: 2
• Total formula weight: 41193.35

Authors

Chen, L.,DiGiammarino, E.,Zhou, X.E.,Wang, Y.,Toh, D.,Hodge, T.W.,Meehan, E.J. (deposition date: 2004-07-16, release date: 2004-09-14, Last modification date: 2023-10-25)

Primary citation

Chen, L.,DiGiammarino, E.,Zhou, X.E.,Wang, Y.,Toh, D.,Hodge, T.W.,Meehan, E.J.
High resolution crystal structure of human Rab9 GTPase: A novel antiviral drug target
J.Biol.Chem., 279:40204-40208, 2004

PubMed Abstract: 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.

PubMed: 15263003
DOI: 10.1074/jbc.M407114200

Experimental method

X-RAY DIFFRACTION (1.25 Å)