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Catalytic Site Atlas

CSA LITERATURE entry for 1g99

E.C. nameacetate kinase
SpeciesMethanosarcina thermophila ()
E.C. Number (IntEnz) 2.7.2.1
CSA Homologues of 1g99There are 10 Homologs
CSA Entries With UniProtID P38502
CSA Entries With EC Number 2.7.2.1
PDBe Entry 1g99
PDBSum Entry 1g99
MACiE Entry 1g99

Literature Report

IntroductionAcetate kinase is a key enzyme for many methanogenic bacteria as it is able to catalyse the interconversion of Acetate and Acetyl phosphate using the removal of a phosphate from ATP. Structural analysis of the enzyme from Methanosarcina thermophila, an Archaea, shows that it is a member of the sugar kinase superfamily which includes hexokinase, and geochemical studies suggest that it is most likely to be the urkinase- the ancestor of all of the members of the superfamily.
MechansimThe reaction seems to take place by an in-line single displacement reaction where the acetate acts as the nucleophile to attack the gamma phosphate of ATP, resulting in Acetyl phosphate and ADP. For this reaction to occur, acetate must be maintained deprotonated, accomplished despite the hydrophobic environment by Asp 148, and the pentavalent phosphate intermediate must be stabilised, a role carried out by Arg 91, Arg 241 and the carbonyl group of Gly 212, as well as Mg2+ and Ser 10.
Reaction

Catalytic Sites for 1g99

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GlyA212212macie:mainChainAmideContacts beta phosphate of ATP thus stabilises the pentavalent phosphate transition state.
SerA1010macie:sideChainContacts beta phosphate of ATP thus stabilises the pentavalent phosphate transition state.
AspA148148macie:sideChainMaintains acetate in a deprotonated state despite hydrophobic environment to allow it to act as nucleophile and attack the gamma phosphate.
ArgA9191macie:sideChainContacts alpha phosphate of ATP along with Arg 241 thus stabilises the pentavalent phosphate transition state through electrostatic interactions.
ArgA241241macie:sideChainContacts alpha phosphate of ATP along with Arg 91, thus stabilises the pentavalent phosphate transition state.

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GlyB212212macie:mainChainAmideContacts beta phosphate of ATP thus stabilises the pentavalent phosphate transition state.
SerB1010macie:sideChainContacts beta phosphate of ATP thus stabilises the pentavalent phosphate transition state.
AspB148148macie:sideChainMaintains acetate in a deprotonated state despite hydrophobic environment to allow it to act as nucleophile and attack the gamma phosphate.
ArgB9191macie:sideChainContacts alpha phosphate of ATP along with Arg 241 thus stabilises the pentavalent phosphate transition state through electrostatic interactions.
ArgB241241macie:sideChainContacts alpha phosphate of ATP along with Arg 91, thus stabilises the pentavalent phosphate transition state.

Literature References

Notes:
Buss KA
Urkinase: structure of acetate kinase, a member of the ASKHA superfamily of phosphotransferases.
J Bacteriol 2001 183 680-686
PubMed: 11133963
Miles RD
Site-directed mutational analysis of active site residues in the acetate kinase from Methanosarcina thermophila.
J Biol Chem 2001 276 45059-45064
PubMed: 11562377
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