Alpha/beta‐hydrolases: A unique structural motif coordinates catalytic acid residue in 40 protein fold families

@article{Dimitriou2017AlphabetahydrolasesAU,
  title={Alpha/beta‐hydrolases: A unique structural motif coordinates catalytic acid residue in 40 protein fold families},
  author={Polytimi S Dimitriou and Alexander I. Denesyuk and Seiji Takahashi and Satoshi Yamashita and Mark S. Johnson and Toru Nakayama and Konstantin A. Denessiouk},
  journal={Proteins: Structure},
  year={2017},
  volume={85},
  pages={1845 - 1855}
}
The alpha/beta‐hydrolases are a family of acid‐base‐nucleophile catalytic triad enzymes with a common fold, but using a wide variety of substrates, having different pH optima, catalyzing unique catalytic reactions and often showing improved chemical and thermo stability. The ABH enzymes are prime targets for protein engineering. Here, we have classified active sites from 51 representative members of 40 structural ABH fold families into eight distinct conserved geometries. We demonstrate the… 
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References

SHOWING 1-10 OF 66 REFERENCES
Bioinformatic analysis of alpha / beta-hydrolase fold enzymes reveals subfamily-specific positions responsible for discrimination of amidase and lipase activities †
Superfamily of alpha-beta hydrolases is one of the largest groups of structurally related enzymes with diverse catalytic functions. Bioinformatic analysis was used to study how lipase and amidase
Enzymatic activity and protein interactions in alpha/beta hydrolase fold proteins: moonlighting versus promiscuity.
TLDR
This review surveys some of the best-known examples of multiple functions in alpha/beta hydrolase fold proteins, an important tinkering tool kit for protein function evolution.
Catalytic triad of microsomal epoxide hydrolase: replacement of Glu404 with Asp leads to a strongly increased turnover rate.
TLDR
Owing to its enhanced catalytic properties, the Glu404-->Asp mutant might represent a versatile tool for the enantioselective bio-organic synthesis of chiral fine chemicals.
Multiple Conformations of Catalytic Serine and Histidine in Acetylxylan Esterase at 0.90 Å*
TLDR
The exposed nature of the catalytic triad suggests that AXEII is a pure esterase,i.e. an α/β hydrolase with specificity for nonlipidic polar substrates.
Crystal structure of hydroxynitrile lyase from Sorghum bicolor in complex with the inhibitor benzoic acid: a novel cyanogenic enzyme.
TLDR
A mechanism involving general base catalysis by the carboxy-terminal Trp270 carboxyl group and proton transfer toward the leaving nitrile group by an active site water molecule is proposed.
Structure of the minimized alpha/beta-hydrolase fold protein from Thermus thermophilus HB8.
TLDR
Results suggest that TTHA1544 represents the minimized alpha/beta-hydrolase fold and that an additional component would be required for its activity.
Novel Zinc-binding Center and a Temperature Switch in theBacillus stearothermophilus L1 Lipase*
TLDR
The structure of a thermoalkalophilic lipase from Bacillus stearothermophilusL1 (L1 lipase) determined at 2.0-Å resolution shows a zinc-binding site in an extra domain that accounts for the larger molecular size of the family I.5 enzymes in comparison to other microbial lipases.
Structural Basis for Dimerization and Catalysis of a Novel Esterase from the GTSAG Motif Subfamily of the Bacterial Hormone-sensitive Lipase Family*
TLDR
The structural basis for dimerization and catalysis of an esterase from the GTSAG motif subfamily of the HSL family is revealed and sheds light on protein folding and evolution of HSLs.
Structure, biochemical characterization and analysis of the pleomorphism of carboxylesterase Cest‐2923 from Lactobacillus plantarum WCFS1
TLDR
It is discovered that Cest‐2923 exhibits a pH‐dependent pleomorphic behaviour in solution involving monomers, canonical dimers and tetramers, which is similar to that of other carboxylesterases from the hormone‐sensitive lipase family.
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