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Catalytic Site Atlas

CSA LITERATURE entry for 1kc7

E.C. namepyruvate, phosphate dikinase
SpeciesClostridium symbiosum (Bacteria)
E.C. Number (IntEnz) 2.7.9.1
CSA Homologues of 1kc7There are 14 Homologs
CSA Entries With UniProtID P22983
CSA Entries With EC Number 2.7.9.1
PDBe Entry 1kc7
PDBSum Entry 1kc7
MACiE Entry M0207

Literature Report

IntroductionPyruvate phosphate dikinase (PPDK) catalyses the interconversion of ATP, Pi , and pyruvate with AMP, PPi , and PEP .
There are three catalytic domains in C. Symbiosum PPDK; Steps I and II take place in the active site formed at the interface of the N-terminal domain (which binds Mg2+, ATP, and Ppi) and the central domain (which contributes the catalytic His455) in PPDK conformer 1. Step III takes place in the active site formed at the interface of the C-terminal domain (which binds Mg2+ and pyruvate) and the central domain (which contributes the phosphorylated His455) in PPDK conformer 2.
MechansimPhosphoryl transfer is mediated by a carrier histidine, this His455 attacks the beta phosphate of the ATP in a nucleophilic substitution that results in His455 carrying a pyrophosphate moiety and the AMP product. Free phosphate attacks the terminal phosphate of the His455 pyrophosphate moiety in a nucleophilic substitution, resulting in free pyrophosphate and phosphorylated His455. In a proton relay chain involving bulk solvent, Tyr851, water, Ser764 and Cys831 the CH3 group of the pyruvate substrate is deprotonated. This initiates a double bond rearrangement that causes the ketone carbonyl group to attack the phosphorylated His455 in a nucleophilic substitution generating free His455 and the final product.
Note magnesium divalent ions are involved in the reaction, however specific purpose and position have not yet been determined experimentally.
Reaction

Catalytic Sites for 1kc7

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisA455455macie:sideChainHis455 is the phosphate carrier and initiates nucleophilic substitution on the beta phosphate of ATP leading to His455 carrying a pyrophosphate moiety. In the final step the ketone carbonyl group attacks phosphorylated His455 to generate His455 and phosphoenolpyruvate.
MetA103103macie:sideChainForms oxyanion hole in the initial attack of His455 on beta-phosphate.
GlyA101101macie:mainChainAmideForms oxyanion hole in the initial attack of His455 on beta-phosphate.
LysA2222macie:sideChainElectrostatically stabilises the transition state in the formation of pyrophosphorylated His residue.
ArgA337337macie:sideChainElectrostatically stabilises the transition state int eh formation of pyrophosphorylated His455.
CysA831831macie:sideChainActs as a general base to deprotonate methyl group of pyruvate substrate- then forms part of proton shuttle.
SerA764764macie:sideChainReceives proton from Cys831 and transports to Tyr851. Proton shuttle.
TyrA851851macie:sideChainEnd of proton shuttle, transfers proton to solvent.

Literature References

Notes:
Herzberg O
Pyruvate site of pyruvate phosphate dikinase: crystal structure of the enzyme-phosphonopyruvate complex, and mutant analysis.
Biochemistry 2002 41 780-787
PubMed: 11790099
McGuire M
Location of the phosphate binding site within Clostridium symbiosum pyruvate phosphate dikinase.
Biochemistry 1998 37 13463-13474
PubMed: 9753432
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