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A critical survey of average distances between catalytic carboxyl groups in glycoside hydrolases

Authors

  • Ndumiso N. Mhlongo,

    1. Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
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  • Adam A. Skelton,

    1. Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
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  • Gert Kruger,

    1. Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
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  • Mahmoud E.S. Soliman,

    Corresponding author
    1. Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
    • Correspondence to: M.E.S. Soliman, School of Health Sciences, University of KwaZulu-Natal, Durban 4001, South Africa. E-mail: soliman@ukzn.ac.za and I.H. Williams, Department of Chemistry, University of Bath, Bath BA2 7AY, United Kingdom. E-mail: i.h.williams@bath.ac.uk

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  • Ian H. Williams

    Corresponding author
    1. Department of Chemistry, University of Bath, Bath, United Kingdom
    • Correspondence to: M.E.S. Soliman, School of Health Sciences, University of KwaZulu-Natal, Durban 4001, South Africa. E-mail: soliman@ukzn.ac.za and I.H. Williams, Department of Chemistry, University of Bath, Bath BA2 7AY, United Kingdom. E-mail: i.h.williams@bath.ac.uk

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ABSTRACT

Published X-ray crystallographic structures for glycoside hydrolases (GHs) from 39 different families are surveyed according to some rigorous selection criteria, and the distances separating 208 pairs of catalytic carboxyl groups (20 α-retaining, 87 β-retaining, 38 α-inverting, and 63 β-inverting) are analyzed. First, the average of all four inter-carboxyl OO distances for each pair is determined; second, the mean of all the pair-averages within each GH family is determined; third, means are determined for groups of GH families. No significant differences are found for free structures compared with those complexed with a ligand in the active site of the enzyme, nor for α-GHs as compared with β-GHs. The mean and standard deviation (1σ) of the unimodal distribution of average OO distances for all families of inverting GHs is 8 ± 2Å, with a very wide range from 5Å (GH82) to nearly 13Å (GH46). The distribution of average OO distances for all families of retaining GHs appears to be bimodal: the means and standard deviations of the two groups are 4.8 ± 0.3Å and 6.4 ± 0.6Å. These average values are more representative, and more likely to be meaningful, than the often-quoted literature values, which are based on a very small sample of structures. The newly-updated average values proposed here may alter perceptions about what separations between catalytic residues are “normal” or “abnormal” for GHs. Proteins 2014; 82:1747–1755. © 2014 Wiley Periodicals, Inc.

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