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Catalytic Site Atlas Search Results
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Catalytic Site Atlas

CSA LITERATURE entry for 1ksj

E.C. name3',5'-cyclic-nucleotide phosphodiesterase
SpeciesHomo sapiens (Human)
E.C. Number (IntEnz) 3.1.4.17
CSA Homologues of 1ksjThere are 590 Homologs
CSA Entries With UniProtID
CSA Entries With EC Number 3.1.4.17
PDBe Entry 1ksj
PDBSum Entry 1ksj
MACiE Entry 1ksj

Literature Report

IntroductionThe 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.
MechansimGTP 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.
Reaction

Catalytic Sites for 1ksj

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GlnA7070macie:sideChainActivates water through hydrogen bonding to allow it to act as a nucleophile and hydrolyse the gamma phosphate of GTP releasing GDP and Pi.

Literature References

Notes:
Hanzal-Bayer M
The complex of Arl2-GTP and PDE delta: from structure to function.
EMBO J 2002 21 2095-2106
PubMed: 11980706
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