Structural insights into human microsomal epoxide hydrolase by combined homology modeling, molecular dynamics simulations, and molecular docking calculations

Saenz Mendez, PatriciaGothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology,Universidad de la Republica, URY; Göteborgs Universitet (författare)

A new homology model of human microsomal epoxide hydrolase was derived based on multiple templates. The model obtained was fully evaluated, including MD simulations and ensemble-based docking, showing that the quality of the structure is better than that of only previously known model. Particularly, a catalytic triad was clearly identified, in agreement with the experimental information available. Analysis of intermediates in the enzymatic mechanism led to the identification of key residues for substrate binding, stereoselectivity, and intermediate stabilization during the reaction. In particular, we have confirmed the role of the oxyanion hole and the conserved motif (HGXP) in epoxide hydrolases, in excellent agreement with known experimental and computational data on similar systems. The model obtained is the first one that fully agrees with all the experimental observations on the system. (C) 2017 Wiley Periodicals, Inc.

Katz, A.Göteborgs Universitet (författare)
Perez-Kempner, M. L.Göteborgs Universitet (författare)
Ventura, O. N.Universidad de la Republica, URY (författare)
Vazquez, M. (författare)
Göteborgs universitetInstitutionen för kemi och molekylärbiologi (creator_code:org_t)

Ingår i:Proteins-Structure Function and Bioinformatics: Wiley85:4, s. 720-7300887-35851097-0134

Av författaren/redakt...: Saenz Mendez, Pa ...; Katz, A.; Perez-Kempner, M ...; Ventura, O. N.; Vazquez, M.

Om ämnet

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.