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Catalytic Site Atlas Version 2.2.12
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CSA entry for 1ksj
Original Entry
Title:
Signaling protein/hydrolase
Compound:
Arf-like protein 2
Mutant:
No
UniProt/Swiss-Prot:
O43924-CNRD_HUMAN
Q9D0J4-Q9D0J4
EC Class:
3.1.4.17
Other CSA Entries:
Overview of all sites for 1ksj
Homologues of 1ksj
Entries for UniProt/Swiss-Prot: O43924
Entries for UniProt/Swiss-Prot: Q9D0J4
Entries for EC: 3.1.4.17
Other Databases:
PDB entry: 1ksj
PDBsum entry: 1ksj
UniProt/Swiss-Prot: O43924
UniProt/Swiss-Prot: Q9D0J4
IntEnz entry: 3.1.4.17
Literature Report:
Introduction:
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.
Mechanism:
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.
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Found by:
Literature reference 

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
SA 13 13
NucleophileSubstrate
Acts as nucleophile to hydrolyse GTP releasing GDP and Pi.
Evidence from paper Evidence concerns Evidence type
PubMed ID 11980706 Current protein Conservation of residue
PubMed ID 11980706 Current protein Residue is positioned appropriately (ligand position known)

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
GLNA 70 70Sidechain
ElectrostaticWater
Activates water through hydrogen bonding to allow it to act as a nucleophile and hydrolyse the gamma phosphate of GTP releasing GDP and Pi.
Evidence from paper Evidence concerns Evidence type
PubMed ID 11980706 Current protein Residue is positioned appropriately (ligand position known)
PubMed ID 11980706 Current protein Structural similarity to homologue of known mechanism

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
MGA 205 0
ElectrostaticTransition state
Is able to stabilise the pentavalent phosphate transition state through favourable electrostatic contacts with the gamma phosphate of GTP.
Evidence from paper Evidence concerns Evidence type
PubMed ID 11980706 Current protein Structural similarity to homologue of known mechanism
PubMed ID 11980706 Current protein Ligand is essential for catalysis
References:
1
The complex of Arl2-GTP and PDE delta: from structure to function.
M. Hanzal-Bayer and L. Renault and P. Roversi and A. Wittinghofer and R. C. Hillig
EMBO J 21, (9) 2095-106, (2002).
11980706
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