PDBsum entry 1wms

Protein transport

PDB id: 1wms

Contents

Protein chains

170 a.a. *

Ligands

GDP ×2

Waters ×508

* Residue conservation analysis

PDB id:

1wms

Name:

Protein transport

Title:

High resolution crystal structure of human rab9 gtpase: a novel antiviral drug target

Structure:

Ras-related protein rab-9a. Chain: a, b. Fragment: c-terminal truncated. Synonym: rab-9, rab9. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: rab9. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Dimer (from PQS)

Resolution:

1.25Å R-factor: 0.141 R-free: 0.196

Authors:

L.Chen,E.Digiammarino,X.E.Zhou,Y.Wang,D.Toh,T.W.Hodge,E.J.Meehan

Key ref:

L.Chen et al. (2004). High resolution crystal structure of human Rab9 GTPase: a novel antiviral drug target. J Biol Chem, 279, 40204-40208. PubMed id: 15263003 DOI: 10.1074/jbc.M407114200

Date:

16-Jul-04 Release date: 14-Sep-04

Protein chains

P51151  (RAB9A_HUMAN) -  Ras-related protein Rab-9A from Homo sapiens

Seq: 201 a.a.

Struc: 170 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1074/jbc.M407114200

J Biol Chem 279:40204-40208 (2004)

PubMed id: 15263003

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

L.Chen, E.DiGiammarino, X.E.Zhou, Y.Wang, D.Toh, T.W.Hodge, E.J.Meehan.

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.

Selected figure(s)

Figure 2.
FIG. 2. Stereoview of the C race of Rab9. Every 10th residue and both N and C termini are labeled. Residues 1, 35-38, and 176-177 are missing from the refined model and are not shown.

Figure 5.
FIG. 5. Structure-based sequence alignment of Rab9 with the most similar structures. The sequence number for the first residue of each line is indicated on the left. The positions of the secondary structural elements in Rab9 are indicated by underlining the sequence and labeling as in Fig. 1. Residues that are highly conserved in the Rab GTPase family are indicated in boldface type. Residues that are known to contact GDP in protein-GDP complex structures are indicated in red. Additional residues that would interact with the -phosphate in protein-GTP analog complex structures are shown in purple. The seven regions that show high degree of conformational variation among the superimposed structures (see Fig. 6) are highlighted in gold and labeled. See Table III for protein abbreviations and references.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 40204-40208) copyright 2004.

Figures were selected by an automated process.