Journal Article

FZJ-2018-00528

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Determinants and Prediction of Esterase Substrate Promiscuity Patterns

Martínez-Martínez, M. ; Coscolín, C. ; Santiago, G. ; Chow, J. ; Stogios, P. J. ; Bargiela, R. ; Gertler, C. ; Navarro-Fernández, J. ; Bollinger, A.FZJ* ; Thies, S.FZJ* ; Méndez-García, C. ; Popovic, A. ; Brown, G. ; Chernikova, T. N. ; García-Moyano, A. ; Bjerga, G. E. K. ; Pérez-García, P. ; Hai, T. ; Del Pozo, M. V. ; Stokke, R. ; Steen, I. H. ; Cui, H. ; Xu, X. ; Nocek, B. P. ; Alcaide, M. ; Distaso, M. ; Mesa, V. ; Peláez, A. I. ; Sánchez, J. ; Buchholz, P. C. F. ; Pleiss, J. ; Fernández-Guerra, A. ; Glöckner, F. O. ; Golyshina, O. V. ; Yakimov, M. M. ; Savchenko, A. ; Jaeger, K.-E.FZJ* ; Yakunin, A. F. ; Streit, W. R. ; Golyshin, P. N. ; Guallar, V. (Corresponding author) ; Ferrer, M. (Corresponding author)

2018
Soc. Washington, DC

This record in other databases:      

Please use a persistent id in citations: doi:10.1021/acschembio.7b00996

Abstract: Esterases receive special attention because of their wide distribution in biological systems and environments and their importance for physiology and chemical synthesis. The prediction of esterases’ substrate promiscuity level from sequence data and the molecular reasons why certain such enzymes are more promiscuous than others remain to be elucidated. This limits the surveillance of the sequence space for esterases potentially leading to new versatile biocatalysts and new insights into their role in cellular function. Here, we performed an extensive analysis of the substrate spectra of 145 phylogenetically and environmentally diverse microbial esterases, when tested with 96 diverse esters. We determined the primary factors shaping their substrate range by analyzing substrate range patterns in combination with structural analysis and protein–ligand simulations. We found a structural parameter that helps rank (classify) the promiscuity level of esterases from sequence data at 94% accuracy. This parameter, the active site effective volume, exemplifies the topology of the catalytic environment by measuring the active site cavity volume corrected by the relative solvent accessible surface area (SASA) of the catalytic triad. Sequences encoding esterases with active site effective volumes (cavity volume/SASA) above a threshold show greater substrate spectra, which can be further extended in combination with phylogenetic data. This measure provides also a valuable tool for interrogating substrates capable of being converted. This measure, found to be transferred to phosphatases of the haloalkanoic acid dehalogenase superfamily and possibly other enzymatic systems, represents a powerful tool for low-cost bioprospecting for esterases with broad substrate ranges, in large scale sequence data sets.

---

Contributing Institute(s):

1. Institut für Molekulare Enzymtechnologie (HHUD) (IMET)

Research Program(s):

1. 581 - Biotechnology (POF3-581) (POF3-581)

Appears in the scientific report 2018

---

Database coverage:
; BIOSIS Previews ; Current Contents - Life Sciences ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

---