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CSA LITERATURE entry for 2lpr

E.C. namealpha-lytic endopeptidase
SpeciesLysobacter enzymogenes ()
E.C. Number (IntEnz)
CSA Homologues of 2lpr
CSA Entries With UniProtID P00778
CSA Entries With EC Number
PDBe Entry 2lpr
PDBSum Entry 2lpr
MACiE Entry 2lpr

Literature Report

IntroductionAlpha-lytic protease from Lysobacter enzymogenes is a serine protease. It hydrolyses proteins with specificity to L-ala and L-val residues in such things as bacterial cell walls and elastin. It belongs to the peptidase S1E family.
Mechansim1. The substrate carbonyl is activated by the positively charged oxyanion hole formed by the backbone NH's of Gly 193 and Ser 195. 2. His 57 acts as a general base to activate Ser 195, which then goes on to nucleophilically attack the substrate carbonyl, forming a tetrahedral intermediate. 3. The resulting protonated His 57 is stabilised by hydrogen bond to Asp 102. 4. The negatively charged intermediate is stabilised by interaction with the backbone NH's of Gly 193 and Ser 195 of the oxyanion hole. 5. The tetrahedral intermediate collapses with expulsion of the leaving group, assisted by protonated His 57 acting as a general acid, to yield the acylenzyme intermediate. 6. His 57 acts as a general base to a water molecule which nucleophilically attacks the acylenzyme, forming a second tetrahedral intermediate (again stabilised by the oxyanion hole.) 7. This intermediate collapses, expelling Ser 195 as the leaving group, assisted by the protonated His 57 acting as a general acid, and forming the carboxylic acid product.

Catalytic Sites for 2lpr

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspA102262macie:sideChainThe Asp 102 carboxylate stabilises the protonated His 57 residue.
GlyA193340macie:mainChainAmideThe backbone NH (along with the backbone of Ser 195) forms the oxyanion hole. The positive charge activates the substrate carbonyl and also stabilises the negatively charged intermediate.
HisA57235macie:sideChainHis 57 activates Ser 195 by deprotonating it. It then donates a proton to the leaving group. His 57 then deprotonates water, which goes on to nucleophilically attack the substrate carbonyl. Finally, it donates a proton back to Ser 195 as the Ser 195 - substrate bond is broken.

Literature References

Bone R
Serine protease mechanism: structure of an inhibitory complex of alpha-lytic protease and a tightly bound peptide boronic acid.
Biochemistry 1987 26 7609-7614
PubMed: 3122831
Hedstrom L.
Serine protease mechanism and specificity.
Chem Rev 2002 102 4501-4524
PubMed: 12475199