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| {{STRUCTURE_1wms| PDB=1wms | SCENE= }} | | {{STRUCTURE_1wms| PDB=1wms | SCENE= }} |
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| '''High resolution crystal structure of human Rab9 GTPase: a novel antiviral drug target'''
| | ===High resolution crystal structure of human Rab9 GTPase: a novel antiviral drug target=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_15263003}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 15263003 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_15263003}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Zhou, X E.]] | | [[Category: Zhou, X E.]] |
| [[Category: Gtpase]] | | [[Category: Gtpase]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 13:53:15 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 04:23:57 2008'' |
