What question did this study set out to answer?

To determine the structural and molecular basis underlying the atypical elastolytic substrate specificity observed in rodent alpha-chymase HAM2.

November 1, 2007Journal of Biological ChemistryOpen Access

Structural Basis for Elastolytic Substrate Specificity in Rodent α-Chymases

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Authors

JKJukka KervinenFraunhofer USA Center for Molecular Biotechnology MAM.C. AbadJikei University School of Medicine CCCarl CryslerJohnson & Johnson (United States)

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Implication

Crystallographic analysis reveals elastolytic substrate specificity in rodent chymase-2, indicating that a conserved structural triplet directs enzyme evolutionary divergence.

Key Points

To determine the structural and molecular basis underlying the atypical elastolytic substrate specificity observed in rodent alpha-chymase HAM2.
Characterized and compared the hydrolytic and proteolytic substrate preferences of hamster chymase-1 (HAM1) and hamster chymase-2 (HAM2).
Solved the 2.5-Å resolution crystal structure of HAM2 complexed with the peptidyl chloromethylketone inhibitor MeOSuc-Ala-Ala-Pro-Ala-CMK.
Conducted sequence alignments and phylogenetic analyses across rodent, rabbit, and guinea pig chymases.
HAM2 demonstrated atypical elastolytic cleavage on the carboxyl side of small hydrophobic P1 residues (Ala and Val), whereas HAM1 exhibited standard chymotryptic activity.
The 2.5-Å crystal structure demonstrated that mutations at positions 189, 190, 216, and 226 generate a constricted, shallow S1 binding pocket capable of fitting only small hydrophobic side chains.
Identified a conserved Asn189-Val190-Val216 residue triplet unique to rodent alpha-chymases that predicts elastolytic specificity in uncharacterized chymase-like enzymes.

Cite This Study

Kervinen et al. (2007) studied this question.

synapsesocial.com/papers/6a76f596df493903fd1e8ec9 https://doi.org/10.1074/jbc.m707157200

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Implication

Crystallographic analysis reveals elastolytic substrate specificity in rodent chymase-2, indicating that a conserved structural triplet directs enzyme evolutionary divergence.

Structural Basis for Elastolytic Substrate Specificity in Rodent α-Chymases

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Implication

Key Points

Cite This Study

Structural Basis for Elastolytic Substrate Specificity in Rodent α-Chymases

Discussion

Member takes

Implication

Key Points

Cite This Study

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