Toggle Main Menu Toggle Search

Open Access padlockePrints

Cognate ligand domain mapping for enzymes

Lookup NU author(s): Dr Matthew BashtonORCiD


Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Here, we present an automatic assignment of potential cognate ligands to domains of enzymes in the CATH and SCOP protein domain classifications on the basis of structural data available in the wwPDB. This procedure involves two steps; firstly, we assign the binding of particular ligands to particular domains; secondly, we compare the chemical similarity of the PDB ligands to ligands in KEGG in order to assign cognate ligands. We find that use of the Enzyme Commission (EC) numbers is necessary to enable efficient and accurate cognate ligand assignment. The PROCOGNATE database currently has cognate ligand mapping for 3277 (4118) protein structures and 351 (302) superfamilies, as described by the CATH and (SCOP) databases, respectively. We find that just under half of all ligands are only and always bound by a single domain, with 16% bound by more than one domain and the remainder of the ligands showing a variety of binding modes. This finding has implications for domain recombination and the evolution of new protein functions. Domain architecture or context is also found to affect substrate specificity of particular domains, and we discuss example cases. The most popular PDB ligands are all found to be generic components of crystallisation buffers, highlighting the non-cognate ligand problem inherent in the PDB. In contrast, the most popular cognate ligands are all found to be universal cellular currencies of reducing power and energy such as NADH, FADH2 and ATP, respectively, reflecting the fact that the vast majority of enzymatic reactions utilise one of these popular co-factors. These ligands all share a common adenine ribonucleotide moiety, suggesting that many different domain superfamilies have converged to bind this chemical framework.

Publication metadata

Author(s): Bashton M, Nobeli I, Thornton JM

Publication type: Article

Publication status: Published

Journal: Journal of Molecular Biology

Year: 2006

Volume: 364

Issue: 4

Pages: 836-852

Print publication date: 08/12/2006

ISSN (print): 0022-2836

ISSN (electronic): 1089-8638

Publisher: Elsevier Ltd. / Academic Press


DOI: 10.1016/j.jmb.2006.09.041

PubMed id: 17034815


Altmetrics provided by Altmetric