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

Polytimi Dimitriou, Alexandre Denesyuk, Seiji Takahashi, Satoshi Yamashita, Mark S Johnson, Toru Nakayama, Konstantin Denessiouk

Tutkimustuotos: LehtiartikkeliArtikkeliTieteellinenvertaisarvioitu

13 Sitaatiot (Scopus)

Abstrakti

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 occurrence of a common structural motif, the catalytic acid zone, at the catalytic triad acid turn. We show that binding of an external ligand does not change the structure of the catalytic acid zone and both the ligand-free and ligand-bound forms of the protein belong to the same catalytic acid zone subgroup. We also show that the catalytic acid zone coordinates the position of the catalytic histidine loop directly above its plane, and consequently, fixes the catalytic histidine in a proper position near the catalytic acid. Finally, we demonstrate that the catalytic acid zone plays a key role in multi-subunit complex formation in ABH enzymes, and is involved in interactions with other proteins. As a result, we speculate that each of the catalytic triad residues has its own supporting structural scaffold, similar to the catalytic acid zone, described above, which together form the extended catalytic triad motif. Each scaffold coordinates the function of its respective catalytic residue, and can even compensate for the loss of protein function, if the catalytic amino acid is mutated.
AlkuperäiskieliEi tiedossa
Sivut1845–1855
JulkaisuProteins
Vuosikerta85
Numero10
DOI - pysyväislinkit
TilaJulkaistu - 2017
OKM-julkaisutyyppiA1 Julkaistu artikkeli, soviteltu

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