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Catalytic Site Atlas

CSA LITERATURE entry for 1rtf

E.C. namet-plasminogen activator
SpeciesHomo sapiens (Human)
E.C. Number (IntEnz)
CSA Homologues of 1rtfThere are 1223 Homologs
CSA Entries With UniProtID P00750
CSA Entries With EC Number
PDBe Entry 1rtf
PDBSum Entry 1rtf
MACiE Entry 1rtf

Literature Report

IntroductionTissue-type plasminogen activator is a serine proteinase of the trypsin-family. It catalyses the activation of the zymogen plasminogen to the fibrin-degrading proteinase plasmin in fibrinolysis.
Human tissue-type plasminogen activator is being studied for therapeutic use in cases such as myocardial infarctions and other thromboembolic disorders.
MechansimTissue-type plasminogen activator employs a classical serine protease mechanism. Ser 195 acts as a nucleophile to attack the peptide bond and form a tetrahedral intermediate that is stabilised by the backbone NH of Ser 195 and Gly 193. His 57 promotes the nucleophilic attack by deprotonating Ser 195, while Asp 102 functions to modify the pKa of His 57. Collapse of the tetrahedral intermediate with protonation of the departing amine leaving group by His 57 generates an acyl-enzyme intermediate. This is then hydrolysed by a water molecule that is deprotonated by His 57.

Catalytic Sites for 1rtf

Annotated By Reference To The Literature - Site 6 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspB102406macie:sideChainModifies the pKa of His 57 to allow it to act as a general acid/base catalyst.
SerB195513macie:sideChainBackbone amide stabilises the transition state and side chain acts as a nucleophile to attack the substrate.
SerB195513macie:mainChainAmideBackbone amide stabilises the transition state and side chain acts as a nucleophile to attack the substrate.
GlyB193511macie:mainChainAmideForms part of the oxyanion hole.
HisB57357macie:sideChainHis 57 acts as a general acid/base catalyst to activate Ser 195 and water to nucleophilic attack and facilitates collapse of the intermediates by proton donation.

Literature References

Lamba D
The 2.3 A crystal structure of the catalytic domain of recombinant two-chain human tissue-type plasminogen activator.
J Mol Biol 1996 258 117-135
PubMed: 8613982