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Catalytic Site Atlas

CSA LITERATURE entry for 1iec

E.C. nameassemblin
SpeciesHuman cytomegalovirus (Human cytomegalovirus)
E.C. Number (IntEnz) 3.4.21.97
CSA Homologues of 1iec
CSA Entries With UniProtID P16753
CSA Entries With EC Number 3.4.21.97
PDBe Entry 1iec
PDBSum Entry 1iec
MACiE Entry M0238

Literature Report

IntroductionHuman cytomegalovirus (HCMV) protease is a serine protease that is involved in the proteolytic processing of the assembly protein precursor during capsid maturation. CMV protease shares no sequence homology with classical serine proteases and contains a Ser-His-His catalytic triad, rather than the classical Ser-His-Asp/Glu. The mechanism, however, is much the same. HCMV protease is involved in autoproteolytic cleavage at two sites to produce an enzyme with full catalytic activity. The enzyme cleaves between Ala-Ala/Ser. HCMV protease exists in a monomer-dimer equilibrium, with the homodimer being active and the monomer not. HCMV protease is a potential antiviral drug target.
MechansimHis63, stabilised by His157, deprotonates Ser132, which can then act as the nucleophile for attack on the carbonyl carbon of the substrate. The tetrahedral intermediate is stabilised by the oxyanion hole. The intermediate collapses and eliminates the product amine, which is protonated by His63. His63 then deprotonates water for nucleophilic attack on the carbonyl carbon of the acyl-enzyme intermediate. The reaction proceeds via a tetrahedral intermediate, stabilised by the oxyanion hole, and then eliminates Ser132, which is protonated by His63.

Catalytic Sites for 1iec

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
ArgA166166macie:sideChainArg166 is part of the oxyanion hole and forms an indirect hydrogen bond to the oxyanion through water.
SerA134134macie:sideChainSer134 is thought to stabilise His157 during the catalytic cycle.
HisA6363macie:sideChainHis63 deprotonates Ser132 to enhance its nucleophilicity and protonates the amine leaving group. It then deprotonates water for attack on the acyl-enzyme intermediate and protonates Ser132 when it acts as a leaving group. His63 forms a hydrogen bond to His157 and the latter stabilises His63 during the catalytic cycle.
AlaA157157macie:sideChainHis157 forms a hydrogen bond to His63 and stabilises the residue during the catalytic cycle. His157 is exposed to the solvent and this limits its functional importance relative to the buried acidic residue in classical serine proteases.
ArgA165165macie:mainChainAmideArg165 forms part of the oxyanion hole and forms a hydrogen bond to the oxyanion.
SebA132132macie:ptmSer132 is deprotonated by His63 and then acts as the nucleophile for attack on the carbonyl carbon of the substrate. Upon intermediate collapse Ser132 forms part of an acyl-enzyme intermediate. During the hydrolysis of this intermediate Ser132 acts as the leaving group and is protonated by His63.

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
ArgA166166macie:sideChainArg166 is part of the oxyanion hole and forms an indirect hydrogen bond to the oxyanion through water.
SerA134134macie:sideChainSer134 is thought to stabilise His157 during the catalytic cycle.
HisA6363macie:sideChainHis63 deprotonates Ser132 to enhance its nucleophilicity and protonates the amine leaving group. It then deprotonates water for attack on the acyl-enzyme intermediate and protonates Ser132 when it acts as a leaving group. His63 forms a hydrogen bond to His157 and the latter stabilises His63 during the catalytic cycle.
AlaA157157macie:sideChainHis157 forms a hydrogen bond to His63 and stabilises the residue during the catalytic cycle. His157 is exposed to the solvent and this limits its functional importance relative to the buried acidic residue in classical serine proteases.
ArgA165165macie:mainChainAmideArg165 forms part of the oxyanion hole and forms a hydrogen bond to the oxyanion.
SebA132132macie:ptmSer132 is deprotonated by His63 and then acts as the nucleophile for attack on the carbonyl carbon of the substrate. Upon intermediate collapse Ser132 forms part of an acyl-enzyme intermediate. During the hydrolysis of this intermediate Ser132 acts as the leaving group and is protonated by His63.

Annotated By Reference To The Literature - Site 3 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
ArgB465165macie:sideChainError
ArgB466166macie:sideChainError
HisB36363macie:sideChainError
AlaB457157macie:sideChainError

Literature References

Notes:
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