1wms
From Proteopedia
(New page: 200px<br /> <applet load="1wms" size="450" color="white" frame="true" align="right" spinBox="true" caption="1wms, resolution 1.25Å" /> '''High resolution cry...) |
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| - | [[Image:1wms.gif|left|200px]]<br /> | + | [[Image:1wms.gif|left|200px]]<br /><applet load="1wms" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1wms" size=" | + | |
caption="1wms, resolution 1.25Å" /> | caption="1wms, resolution 1.25Å" /> | ||
'''High resolution crystal structure of human Rab9 GTPase: a novel antiviral drug target'''<br /> | '''High resolution crystal structure of human Rab9 GTPase: a novel antiviral drug target'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Rab GTPases and their effectors facilitate vesicular transport by | + | 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== | ==About this Structure== | ||
| - | 1WMS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with GDP as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1WMS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=GDP:'>GDP</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WMS OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Chen, L.]] | [[Category: Chen, L.]] | ||
[[Category: DiGiammarino, E.]] | [[Category: DiGiammarino, E.]] | ||
| - | [[Category: Hodge, T | + | [[Category: Hodge, T W.]] |
| - | [[Category: Meehan, E | + | [[Category: Meehan, E J.]] |
[[Category: Toh, D.]] | [[Category: Toh, D.]] | ||
[[Category: Wang, Y.]] | [[Category: Wang, Y.]] | ||
| - | [[Category: Zhou, X | + | [[Category: Zhou, X E.]] |
[[Category: GDP]] | [[Category: GDP]] | ||
[[Category: gtpase]] | [[Category: gtpase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:46:02 2008'' |
Revision as of 13:46, 21 February 2008
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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 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 Thu Feb 21 15:46:02 2008
Categories: Homo sapiens | Single protein | Chen, L. | DiGiammarino, E. | Hodge, T W. | Meehan, E J. | Toh, D. | Wang, Y. | Zhou, X E. | GDP | Gtpase
