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Prediction of distal residue participation in enzyme catalysis
Journal article   Open access   Peer reviewed

Prediction of distal residue participation in enzyme catalysis

Heather R Brodkin, Nicholas A DeLateur, Srinivas Somarowthu, Caitlyn L Mills, Walter R Novak, Penny J Beuning, Dagmar Ringe and Mary Jo Ondrechen
Protein science, v 24(5), pp 762-778
01 May 2015
PMID: 25627867
url
https://doi.org/10.1002/pro.2648View
Published, Version of Record (VoR) Open

Abstract

alkaline phosphatase catalytic efficiency ketosteroid isomerase nitrile hydratase partial order optimum likelihood phosphoglucose isomerase remote residues
A scoring method for the prediction of catalytically important residues in enzyme structures is presented and used to examine the participation of distal residues in enzyme catalysis. Scores are based on the Partial Order Optimum Likelihood (POOL) machine learning method, using computed electrostatic properties, surface geometric features, and information obtained from the phylogenetic tree as input features. Predictions of distal residue participation in catalysis are compared with experimental kinetics data from the literature on variants of the featured enzymes; some additional kinetics measurements are reported for variants of Pseudomonas putida nitrile hydratase (ppNH) and for E scherichia coli alkaline phosphatase (AP). The multilayer active sites of P . putida nitrile hydratase and of human phosphoglucose isomerase are predicted by the POOL log ZP scores, as is the single-layer active site of P . putida ketosteroid isomerase. The log ZP score cutoff utilized here results in over-prediction of distal residue involvement in E. coli alkaline phosphatase. While fewer experimental data points are available for P . putida mandelate racemase and for human carbonic anhydrase II, the POOL log ZP scores properly predict the previously reported participation of distal residues.

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Collaboration types
Domestic collaboration
Web of Science research areas
Biochemistry & Molecular Biology
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