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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1g0d

E.C. nameprotein-glutamine gamma-glutamyltransferase
SpeciesPagrus major (Chrysophrys major)
E.C. Number (IntEnz) 2.3.2.13
CSA Homologues of 1g0dThere are 21 Homologs
CSA Entries With UniProtID P52181
CSA Entries With EC Number 2.3.2.13
PDBe Entry 1g0d
PDBSum Entry 1g0d
MACiE Entry 1g0d

Literature Report

IntroductionFish transglutaminase is able to catalyse the Ca2+ dependent acyl transfer between glutamine and the side chain amino group of lysine. It is unknown what the biological function of this is in fish, but the human homologue is blood clotting factor XIII which forms cross-links between these two residues in fibrin, thus plays a key role in the clotting cascade. The activation of the clotting factor is a subject of study in the hope of designing inhibitors which could be of pharmacological importance.
MechansimThe reaction proceeds in a manner analogous to a cysteine protease: the catalytic Cys 272 acts as the initial nucleophile to attack the carbonyl of the glutamine side chain, resulting in a tetrahedral intermediate. Protonation of the leaving group by His 332, assisted by Asp 355 allows the collapse of this tetrahedral intermediate to form a thiolacyl enzyme intermediate. This intermediate is protected by a Tyr 560 residue in the active form so that Cys 333 cannot form a disulphide to Cys 272 as would otherwise happen. Subsequent nucleophilic attack on the intermediate from a Lysine, activated by deprotonation by His 332, leads to the formation of the product and the release of the Cysteine residue.
Reaction

Catalytic Sites for 1g0d

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
CysA272272macie:sideChainActs as the nucleophile to attack the substrate forming the oxyanion intermediate which collapses to form the thioacyl enzyme intermediate. This in turn breaks down to release the Cysteine, through attack of a Lysine residue from the substrate, forming a crosslinkage.
CysA272272macie:mainChainAmideActs as the nucleophile to attack the substrate forming the oxyanion intermediate which collapses to form the thioacyl enzyme intermediate. This in turn breaks down to release the Cysteine, through attack of a Lysine residue from the substrate, forming a crosslinkage.
AspA355355macie:sideChainForms the third part of the catalytic triad, thus alters the pKa of His 332 so that it can act as an acid-base.
HisA332332macie:sideChainProtonates the leaving group to allow collapse of the tetrahedral intermediate. Then deprotonates the lysine residue from the protein to allow it to act as a nucleophile to break down the covalent intermediate.
TyrA515515macie:sideChainIn the active form, Ca2+ causes Tyr 515 to move so that it prevents Cys 333 from forming a disulphide to the nucleophilic Cys 272; thus can be described as stabilising the thioacyl enzyme intermediate or as activating Cys 272.

Literature References

Notes:
Noguchi K
Crystal structure of red sea bream transglutaminase.
J Biol Chem 2001 276 12055-12059
PubMed: 11080504
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