Author ORCID Identifier
Document Type
Article
Publication Date
2-14-2009
Abstract
To study the substrate specificity of enzymes, we use the amidohydrolase and enolase superfamilies as model systems; members of these superfamilies share a common TIM barrel fold and catalyze a wide range of chemical reactions. Here, we describe a collaboration between the Enzyme Specificity Consortium (ENSPEC) and the New York SGX Research Center for Structural Genomics (NYSGXRC) that aims to maximize the structural coverage of the amidohydrolase and enolase superfamilies. Using sequence- and structure-based protein comparisons, we first selected 535 target proteins from a variety of genomes for high-throughput structure determination by X-ray crystallography; 63 of these targets were not previously annotated as superfamily members. To date, 20 unique amidohydrolase and 41 unique enolase structures have been determined, increasing the fraction of sequences in the two superfamilies that can be modeled based on at least 30% sequence identity from 45% to 73%. We present case studies of proteins related to uronate isomerase (an amidohydrolase superfamily member) and mandelate racemase (an enolase superfamily member), to illustrate how this structure-focused approach can be used to generate hypotheses about sequence-structure-function relationships.
Keywords
amidohydrolase and enolase superfamilies, structural genomics, structure annotation, target selection
Publication Title
Journal of Structural and Functional Genomics
Rights
© 2009 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution Noncommercial License (https://creativecommons.org/licenses/by-nc/2.0), which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
Recommended Citation
Pieper, U., Chiang, R., Seffernick, J.J. et al. Target selection and annotation for the structural genomics of the amidohydrolase and enolase superfamilies. J Struct Funct Genomics 10, 107–125 (2009). https://doi.org/10.1007/s10969-008-9056-5