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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1hpl

E.C. nametriacylglycerol lipase
SpeciesEquus caballus (Horse)
E.C. Number (IntEnz) 3.1.1.3
CSA Homologues of 1hpl
CSA Entries With UniProtID P29183
CSA Entries With EC Number 3.1.1.3
PDBe Entry 1hpl
PDBSum Entry 1hpl
MACiE Entry M0218

Literature Report

IntroductionPancreatic lipase from Equus caballus catalyses the conversion of triacylglycerol to 2-monoacylglycerol and free fatty acids. This occurs in the intestine and plays a key role in dietary fat digestion. This is important as it is converting an insoluble substrate into soluble products.
Mechansim1. The negative charge on Asp 176 acts to affect the pKa of His 263, making it more basic. 2. His 263 acts as a general base, by deprotonating Ser 152, activating it for nucleophilic attack on the carbonyl carbon of the ester bond. 3. This forms a negatively charged tetrahedral intermediate which is stabilised by the oxyanion hole formed by the main chain amides of Phe 77 and Leu 153. 4. As the carbonyl is reformed, the ester bond is broken, the leaving group being protonated by His 263. 5. His 263 then acts as a general base again, this time by deprotonating a water molecule, activating it for nucleophilic attack on the substrate carbonyl. 6. Another negatively charged tetrahedral intermediate is formed, and again is stabilised by the oxyanion hole. 7. As the carbonyl is reformed, the substrate-Ser 152 bond is broken, and Ser 152 is then re-protonated by His 263.
Reaction

Catalytic Sites for 1hpl

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisA263276macie:sideChainActivates Ser 152 by deprotonating it. Donates a proton to the leaving acylglycerol. Activates a water molecule by deprotonating it. Donates a proton back to the leaving group Ser 152.
PheA7790macie:mainChainAmideThe main chain amide of Phe 77 acts to stabilise the negatively charged, tetrahedral intermediates.
AspA176189macie:sideChainThe negatively charged Asp 176 helps to activate His 263 to become more basic.
LeuA153166macie:mainChainAmideThe main chain amide of Leu 153 acts to stabilise the negatively charged, tetrahedral intermediates.

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisB263276macie:sideChainActivates Ser 152 by deprotonating it. Donates a proton to the leaving acylglycerol. Activates a water molecule by deprotonating it. Donates a proton back to the leaving group Ser 152.
PheB7790macie:mainChainAmideThe main chain amide of Phe 77 acts to stabilise the negatively charged, tetrahedral intermediates.
AspB176189macie:sideChainThe negatively charged Asp 176 helps to activate His 263 to become more basic.
LeuB153166macie:mainChainAmideThe main chain amide of Leu 153 acts to stabilise the negatively charged, tetrahedral intermediates.

Literature References

Notes:
Bourne Y
Horse pancreatic lipase. The crystal structure refined at 2.3 A resolution.
J Mol Biol 1994 238 709-732
PubMed: 8182745
Lowe ME.
Molecular mechanisms of rat and human pancreatic triglyceride lipases.
J Nutr 1997 127 549-557
PubMed: 9109604
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