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Catalytic Site Atlas

CSA LITERATURE entry for 1v25

E.C. namelong-chain-fatty-acid---CoA ligase
SpeciesThermus thermophilus (Bacteria)
E.C. Number (IntEnz) 6.2.1.3
CSA Homologues of 1v25
CSA Entries With UniProtID Q6L8F0
CSA Entries With EC Number 6.2.1.3
PDBe Entry 1v25
PDBSum Entry 1v25
MACiE Entry M0198

Literature Report

IntroductionLong chain fatty acid coenzyme-A synthetase (LC-FACS) from Thermus thermophilus participates in the first reaction step of long chain fatty acid degradation. C12 to C22 fatty acids are the substrates of LC-FACS, and it catalyses the conversion of them into fatty-acyl-CoA, creating AMP and pyrophosphate as bi-products. LC-FACS is responsible for physiological regulation of cellular functions, as well as fatty acid degradation.
Mechansim1. Trp 444 hydrogen bonds to the alpha-phosphorus atom, making the alpha-phosphorus electron deficient, and a better electrophile. This is helped by the electrostatic interaction of Mg2+. 2. The carbonyl oxygen of the fatty acid nucleophilically attacks the alpha-phosphorus atom, forming a negatively charged, penta-coordinated intermediate. 3. This intermediate is stabilised through interactions between the O1A atom of the substrate and the indole ring of Trp 444. 4. As the intermediate collapses, the scissile P-O bond is broken, resulting in a fatty-acyl-AMP, and a pyrophosphate leaving group. 5. Lys 439 hydrogen bonds to the carbonyl oxygen atom of the fatty-acyl-AMP, and the O1A atom of the alpha-phosphorus, generating an electron deficient carbonyl carbon, making it more electrophilic. 6. The S atom of CoA nucleophilically attacks the fatty-acyl-AMP carbonyl carbon, breaking the C-O ester bond. This forms the fatty-acyl-CoA product, and a negatively charged AMP, which is stabilised by Lys 439.
Reaction

Catalytic Sites for 1v25

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
LysA439439macie:sideChainActs to make the carbonyl carbon atom of fatty-acyl-AMP more electrophilic. Also stabilises the negatively charged AMP leaving group.
TrpA444444macie:sideChainActs to make the alpha-phosphorus atom more electrophilic. stabilises the negatively charged intermediate.

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
LysB439439macie:sideChainActs to make the carbonyl carbon atom of fatty-acyl-AMP more electrophilic. Also stabilises the negatively charged AMP leaving group.
TrpB444444macie:sideChainActs to make the alpha-phosphorus atom more electrophilic. stabilises the negatively charged intermediate.

Literature References

Notes:
Hisanaga Y
Structural basis of the substrate-specific two-step catalysis of long chain fatty acyl-CoA synthetase dimer.
J Biol Chem 2004 279 31717-31726
PubMed: 15145952
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