Small GTPase superfamily, ARF type

 

The GTP dependent protein Arl-2 is part of a family of close relatives of the Arf proteins. Although the function of the Arf proteins themselves has been determined (they are involved in regulating vesicular transport) the function of the Arl family has not yet been determined. The protein Arl-2 interacts with PDEdelta which is a relative of the important signalling protein Rho, thus suggesting Arl-2 regulates transport by PDEdelta. As Ras interacts with Rho, it is not surprising that the mechanism of GTP hydrolysis employed by Arl-2 is similar to that found in Ras. Therefore study of this protein may shed insight into an area of highly important cancer research.

 

Reference Protein and Structure

Sequences
Q9D0J4 UniProt
O43924 UniProt IPR024156 (Sequence Homologues) (PDB Homologues)
Biological species
Mus musculus (house mouse) Uniprot
PDB
1ksj - Complex of Arl2 and PDE delta, Crystal Form 2 (SeMet) (2.6 Å) PDBe PDBsum 1ksj
Catalytic CATH Domains
3.40.50.300 CATHdb (see all for 1ksj)
Cofactors
Magnesium(2+) (1)
Click To Show Structure

Enzyme Reaction (EC:3.6.5.-)

GTP(4-)
CHEBI:37565ChEBI
+
water
CHEBI:15377ChEBI
→
GDP(3-)
CHEBI:58189ChEBI
+
hydron
CHEBI:15378ChEBI
+
hydrogenphosphate
CHEBI:43474ChEBI

Enzyme Mechanism

Introduction

GTP hydrolysis is achieved through the activation of a conserved water molecule W13 in the active site by Gln 70. The water molecule thus can act as a nucleophile to attack the gamma phosphate of GTP, releasing GDP and Pi. This reaction passes through a pentavalent phosphate intermediate which is stabilised by Mg2+ at the active site.

Catalytic Residues Roles

UniProt PDB* (1ksj)
Gln70 Gln70(72)A Activates water through hydrogen bonding to allow it to act as a nucleophile and hydrolyse the gamma phosphate of GTP releasing GDP and Pi. electrostatic stabiliser
*PDB label guide - RESx(y)B(C) - RES: Residue Name; x: Residue ID in PDB file; y: Residue ID in PDB sequence if different from PDB file; B: PDB Chain; C: Biological Assembly Chain if different from PDB. If label is "Not Found" it means this residue is not found in the reference PDB.

Chemical Components

References

  1. Hanzal-Bayer M et al. (2002), EMBO J, 21, 2095-2106. The complex of Arl2-GTP and PDEdelta: from structure to function. DOI:10.1093/emboj/21.9.2095. PMID:11980706.

Step 1.

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Catalytic Residues Roles

Residue Roles
Gln70(72)A electrostatic stabiliser

Chemical Components

Step 1.

Contributors

Peter Sarkies, Gemma L. Holliday