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Catalytic Site Atlas Search Results
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Catalytic Site Atlas

CSA LITERATURE entry for 1jh6

E.C. nameCYCLIC PHOSPHODIESTERASE
SpeciesArabidopsis thaliana (Thale cress)
E.C. Number (IntEnz) 3.1.4.-
CSA Homologues of 1jh61fsi,1jh7,
CSA Entries With UniProtID
CSA Entries With EC Number 3.1.4.-
PDBe Entry 1jh6
PDBSum Entry 1jh6
MACiE Entry 1jh6

Literature Report

IntroductionDuring the tRNA splicing reaction in eukaryotes, an ADP ribose cyclic phosphate is formed. Hydrolysis of this to regenerate the monoester ADP ribose-1-phosphate is therefore a necessary part of the overall process. The enzyme cyclic phosphodiesterase is able to catalyse this reaction in the organism Arabidopsis thaliania. It displays a unique fold, but has some sequence identity with the equivalent enzymes in both wheat and zebrafish, specifically in the presence of the sequence motif H-X-T-S-X-H in the active site. Mechanistic and active site features in this family of enzymes are also found to be similar to other RNA processing proteins such as RNAase A.
MechansimThe reaction proceeds by nucleophilic attack by a water molecule, activated by His 119, itself primed by Met 117, on the cyclic phosphate substrate. This leads to a pentavalent phosphate transition state stabilised by Thr 44, Tyr 124 and Ser 121, which collapses following protonation by His 42 of the 2'OH group to leave the product ADP ribose-1-phosphate.

Catalytic Sites for 1jh6

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisA4242macie:sideChainProtonates the 2C of the ribose sugar to allow it to act as a leaving group thus facilitating collapse of the pentavalent phosphate transition state.
SerA121121macie:sideChainStabilises the pentavalent phosphate transition state that forms during the reaction.
MetA117117macie:mainChainCarbonylEnsures that His 119 is in the correct protonation state by forming favourable contacts between the carbonyl and the NH group of the Histidine.
HisA119119macie:sideChainActivates water by deprotonating it so that it can act as a nucleophile and attack the cyclic phosphate.
TyrA124124macie:sideChainStabilises the pentavalent phosphate transition state that forms during the reaction.

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisB4242macie:sideChainProtonates the 2C of the ribose sugar to allow it to act as a leaving group thus facilitating collapse of the pentavalent phosphate transition state.
SerB121121macie:sideChainStabilises the pentavalent phosphate transition state that forms during the reaction.
MetB117117macie:mainChainCarbonylEnsures that His 119 is in the correct protonation state by forming favourable contacts between the carbonyl and the NH group of the Histidine.
HisB119119macie:sideChainActivates water by deprotonating it so that it can act as a nucleophile and attack the cyclic phosphate.
TyrB124124macie:sideChainStabilises the pentavalent phosphate transition state that forms during the reaction.

Literature References

Notes:Concerted action of the two histidines rather than sequential action has not been ruled out; this change in mechanism would however not affect the roles of the catalytic residues.
Hofmann A
Structure and mechanism of activity of the cyclic phosphodiesterase of Appr>p, a product of the tRNA splicing reaction.
EMBO J 2000 19 6207-6217
PubMed: 11080166
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