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Catalytic Site Atlas

CSA LITERATURE entry for 2bhg

E.C. nameRNA-directed RNA polymerase
SpeciesFoot-and-mouth disease virus (Virus)
E.C. Number (IntEnz) 2.7.7.48
CSA Homologues of 2bhg1due,1lvb,1q31,2j92,2wv4,2wv5,
CSA Entries With UniProtID P03306
CSA Entries With EC Number 2.7.7.48
PDBe Entry 2bhg
PDBSum Entry 2bhg
MACiE Entry 2bhg

Literature Report

IntroductionFoot-and-Mouth Disease Virus (FMDV) causes an economically devastating disease of domestic livestock. The viral RNA is translated as a single polypeptide precursor and must be cleaved into functional proteins by virally encoded proteases. 10 of the 13 cleavages are performed by the highly conserved FMDV 3C Protease. Foot-and-Mouth Disease 3C Protease catalyses 3 different reactions. It is an RNA polymerase, selectively cleaves Xaa-Gln and Xaa-Glu amide bonds and autocatalytically cleaves itself from the polyprotein of the foot-and-mouth disease virus by hydrolysis of a Lys-Gly amide bond. It can also cleave host cell initiation factor eIF-4G at amide bonds Gly-Arg and Lys-Arg.
MechansimFoot-and-Mouth Disease Virus has a chymotrypsin-like fold and possesses a Cys-His-Asp catalytic triad, in a similar conformation to the Ser-His-Asp.
1: His 46 acts as a general base, deprotonating Cys 163. Cys 163 performs nucleophilic attack on the carbonyl carbon of the amide bond. 2: This results in a tetrahedral transition state. Protonated His 46 is stabilised by electrostatic interactions with Asp 84. Ser 182 stabilises the conformation of Asp 84 3: The tetrahedral transition state collapses, forming an acyl-enzyme and His 46 acts as a general acid, protonating the amide leaving group. 4: His 46 acts as a general base, deprotonating a water molecule. The activated water molecule performs nucleophilic attack upon the acyl enzyme, forming a tetrahedral transition state. 5: The tetrahedral transition state collapses, forming the acid component of the substrate and Cys 163. His 46 acts as a general acid, protonating the leaving group Cys 163.
Reaction

Catalytic Sites for 2bhg

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisA461695macie:sideChain1: His 64 acts as a general base, deprotonating Cys 163. 2: The tetrahedral transition state formed collapses and His 46 acts as a general acid, protonating the amide leaving group. 3: His 46 acts as a general base, deprotonating a water molecule. 4: The tetrahedral transition state formed collapses and His 46 acts as a general acid, protonating the leaving group Cys 163.
SerA1821831macie:sideChainSer 182 stabilises the conformation of Asp 84, allowing it to electrostatically interact with His 46.
AspA841733macie:sideChainAsp 84 stabilises protonated His 46 through electrostatic interactions.
AlaA1631812macie:sideChainCys 163 performs nucleophilic attack on the carbonyl carbon of the amide bond.

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisA461695macie:sideChain1: His 64 acts as a general base, deprotonating Cys 163. 2: The tetrahedral transition state formed collapses and His 46 acts as a general acid, protonating the amide leaving group. 3: His 46 acts as a general base, deprotonating a water molecule. 4: The tetrahedral transition state formed collapses and His 46 acts as a general acid, protonating the leaving group Cys 163.
SerA1821831macie:sideChainSer 182 stabilises the conformation of Asp 84, allowing it to electrostatically interact with His 46.
AspA841733macie:sideChainAsp 84 stabilises protonated His 46 through electrostatic interactions.
AlaA1631812macie:sideChainCys 163 performs nucleophilic attack on the carbonyl carbon of the amide bond.

Annotated By Reference To The Literature - Site 3 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
SerB1821831macie:sideChainError
HisB461695macie:sideChainError
AlaB1631812macie:sideChainError

Literature References

Notes:
Birtley JR
Crystal structure of foot-and-mouth disease virus 3C protease. New insights into catalytic mechanism and cleavage specificity.
J Biol Chem 2005 280 11520-11527
PubMed: 15654079
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