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Catalytic Site Atlas

CSA LITERATURE entry for 2a86

E.C. namepantoate---beta-alanine ligase
SpeciesMycobacterium tuberculosis (Bacteria)
E.C. Number (IntEnz) 6.3.2.1
CSA Homologues of 2a86
CSA Entries With UniProtID P0A5R0
CSA Entries With EC Number 6.3.2.1
PDBe Entry 2a86
PDBSum Entry 2a86
MACiE Entry M0229

Literature Report

IntroductionPantothenate synthetase (PS), isolated from Mycobacterium tuberculosis, catalyses the ATP-dependent condensation between pantoate and beta-alanine to form pantothenate. This is the last step in the biosynthesis of pantothenate, which is required for CoA synthesis. The reaction proceeds by a Bi Uni Uni Bi Ping Pong kinetic mechanism. PS is a potential drug target for the treatment of tuberculosis.
MechansimThe carboxyl oxygen of pantoate attacks the alpha-phosphate of ATP in an in-line nucleophilic attack to give pantoyl adenylate and pyrophosphate. The transition state is stabilised by a number of interactions with residues and with a magnesium ion bound to the three phosphate groups. His47 donates a proton to the pyrophosphate leaving group. The amino group of beta-alanine is the nucleophile for attack on the carbonyl carbon of pantoyl adenylate to give pantothenate and AMP.
Reaction

Catalytic Sites for 2a86

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisA4444macie:sideChainHis44 is hydrogen bonded to the beta-phosphate of ATP and so can stabilise the transition state of the adenylation reaction. It is part of the HIGH motif.
HisA4747macie:sideChainHis47 donates a proton to the pyrophosphate leaving group during adenylation. It also stabilises the transition state of this reaction by hydrogen bonding to the beta-phosphate. It is part of the HIGH motif.
MetA4040macie:mainChainAmideMet 40 forms a hydrogen bond to the alpha-phosphate of ATP in the transition state of the adenylation reaction, thus stabilising it. It may also stabilise the transition state of the second reaction in the same way.
ArgA198198macie:sideChainArg198 interacts with the gamma-phosphate of ATP during the adenylation step and stabilises the transition state.
ArgA198198macie:mainChainAmideArg198 interacts with the gamma-phosphate of ATP during the adenylation step and stabilises the transition state.
SerA197197macie:sideChainSer197 interacts with the gamma-phosphate of ATP during the adenylation step and stabilises the transition state. It is part of the KSMKS motif.
LysA160160macie:sideChainLys160 interacts with the beta-phosphate of ATP during the adenylation step and stabilises the transition state.
SerA196196macie:sideChainSer196 interacts with the gamma-phosphate of ATP during the adenylation step and stabilises the transition state. It is part of the KSMKS motif.

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisB4444macie:sideChainHis44 is hydrogen bonded to the beta-phosphate of ATP and so can stabilise the transition state of the adenylation reaction. It is part of the HIGH motif.
HisB4747macie:sideChainHis47 donates a proton to the pyrophosphate leaving group during adenylation. It also stabilises the transition state of this reaction by hydrogen bonding to the beta-phosphate. It is part of the HIGH motif.
MetB4040macie:mainChainAmideMet 40 forms a hydrogen bond to the alpha-phosphate of ATP in the transition state of the adenylation reaction, thus stabilising it. It may also stabilise the transition state of the second reaction in the same way.
ArgB198198macie:sideChainArg198 interacts with the gamma-phosphate of ATP during the adenylation step and stabilises the transition state.
ArgB198198macie:mainChainAmideArg198 interacts with the gamma-phosphate of ATP during the adenylation step and stabilises the transition state.
SerB197197macie:sideChainSer197 interacts with the gamma-phosphate of ATP during the adenylation step and stabilises the transition state. It is part of the KSMKS motif.
LysB160160macie:sideChainLys160 interacts with the beta-phosphate of ATP during the adenylation step and stabilises the transition state.
SerB196196macie:sideChainSer196 interacts with the gamma-phosphate of ATP during the adenylation step and stabilises the transition state. It is part of the KSMKS motif.

Literature References

Notes:
Wang S
Crystal structure of the pantothenate synthetase from Mycobacterium tuberculosis, snapshots of the enzyme in action.
Biochemistry 2006 45 1554-1561
PubMed: 16460002
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