Convergent evolution of enzyme active sites is not a rare phenomenon.

Gherardini, Pier Federico, Wass, Mark N., Helmer-Citterich, Manuela, Sternberg, Michael J.E. (2007) Convergent evolution of enzyme active sites is not a rare phenomenon. Journal of Molecular Biology, 372 (3). pp. 817-845. ISSN 0022-2836. (doi:10.1016/j.jmb.2007.06.017) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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Official URL
http://dx.doi.org/10.1016/j.jmb.2007.06.017

Abstract

Since convergent evolution of enzyme active sites was first identified in serine proteases, other individual instances of this phenomenon have been documented. However, a systematic analysis assessing the frequency of this phenomenon across enzyme space is still lacking. This work uses the Query3d structural comparison algorithm to integrate for the first time detailed knowledge about catalytic residues, available through the Catalytic Site Atlas (CSA), with the evolutionary information provided by the Structural Classification of Proteins (SCOP) database. This study considers two modes of convergent evolution: (i) mechanistic analogues which are enzymes that use the same mechanism to perform related, but possibly different, reactions (considered here as sharing the first three digits of the EC number); and (ii) transformational analogues which catalyse exactly the same reaction (identical EC numbers), but may use different mechanisms. Mechanistic analogues were identified in 15% (26 out of 169) of the three-digit EC groups considered, showing that this phenomenon is not rare. Furthermore 11 of these groups also contain transformational analogues. The catalytic triad is the most widespread active site; the results of the structural comparison show that this mechanism, or variations thereof, is present in 23 superfamilies. Transformational analogues were identified for 45 of the 951 four-digit EC numbers present within the CSA and about half of these were also mechanistic analogues exhibiting convergence of their active sites. This analysis has also been extended to the whole Protein Data Bank to provide a complete and manually curated list of the all the transformational analogues whose structure is classified in SCOP. The results of this work show that the phenomenon of convergent evolution is not rare, especially when considering large enzymatic families.

Item Type: Article
DOI/Identification number: 10.1016/j.jmb.2007.06.017
Uncontrolled keywords: convergent evolution; active sites; enzyme function; catalytic mechanism; structural comparison
Subjects: Q Science > QP Physiology (Living systems) > QP517 Biochemistry
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Mark Wass
Date Deposited: 06 Jun 2013 13:20 UTC
Last Modified: 29 May 2019 10:16 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/34183 (The current URI for this page, for reference purposes)
Wass, Mark N.: https://orcid.org/0000-0001-5428-6479
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