HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 38, 40204-40208, September 17, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/38/40204    most recent M407114200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, L. Articles by Meehan, E. J. Search for Related Content PubMed PubMed Citation Articles by Chen, L. Articles by Meehan, E. J. Social Bookmarking                      What's this?

High Resolution Crystal Structure of Human Rab9 GTPase

A NOVEL ANTIVIRAL DRUG TARGET^*

Liqing Chen, Enrico DiGiammarino, Xiaoyin E. Zhou, Yujun Wang, Diana Toh, Thomas W. Hodge¶, and Edward J. Meehan||

From the Laboratory for Structural Biology, Department of Chemistry, Graduate Programs of Biotechnology, Chemistry and Materials Science, University of Alabama in Huntsville, Huntsville, Alabama 35899 and ^¶National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia 30333

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-Å resolution. The overall structure shows a characteristic nucleotide binding fold consisting of a six-stranded -sheet surrounded by five -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.

Received for publication, June 24, 2004 , and in revised form, July 16, 2004.

The atomic coordinates and structure factors (code 1WMS) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

^* This work was supported in part by National Science Foundation-Experimental Program to Stimulate Competitive Research, NASA, and a generous gift from an anonymous donor to the Laboratory for Structural Biology, University of Alabama in Huntsville. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^|| To whom correspondence should be addressed. Tel.: 256-824-6533; Fax: 256-824-6349; E-mail: meehane{at}uah.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				D. Aivazian, R. L. Serrano, and S. Pfeffer TIP47 is a key effector for Rab9 localization J. Cell Biol., June 19, 2006; 173(6): 917 - 926. [Abstract] [Full Text] [PDF]

				S. R. Pfeffer Structural Clues to Rab GTPase Functional Diversity J. Biol. Chem., April 22, 2005; 280(16): 15485 - 15488. [Abstract] [Full Text] [PDF]