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Interaction Signatures Stabilizing the NAD(P)-Binding Rossmann Fold: A Structure Network Approach

Bhattacharyya, Moitrayee and Upadhyay, Roopali and Vishveshwara, Saraswathi (2012) Interaction Signatures Stabilizing the NAD(P)-Binding Rossmann Fold: A Structure Network Approach. In: PLOS ONE, 7 (12).

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Official URL: http://dx.doi.org/10.1371/journal.pone.0051676


The fidelity of the folding pathways being encoded in the amino acid sequence is met with challenge in instances where proteins with no sequence homology, performing different functions and no apparent evolutionary linkage, adopt a similar fold. The problem stated otherwise is that a limited fold space is available to a repertoire of diverse sequences. The key question is what factors lead to the formation of a fold from diverse sequences. Here, with the NAD(P)-binding Rossmann fold domains as a case study and using the concepts of network theory, we have unveiled the consensus structural features that drive the formation of this fold. We have proposed a graph theoretic formalism to capture the structural details in terms of the conserved atomic interactions in global milieu, and hence extract the essential topological features from diverse sequences. A unified mathematical representation of the different structures together with a judicious concoction of several network parameters enabled us to probe into the structural features driving the adoption of the NAD(P)-binding Rossmann fold. The atomic interactions at key positions seem to be better conserved in proteins, as compared to the residues participating in these interactions. We propose a ``spatial motif'' and several ``fold specific hot spots'' that form the signature structural blueprints of the NAD(P)-binding Rossmann fold domain. Excellent agreement of our data with previous experimental and theoretical studies validates the robustness and validity of the approach. Additionally, comparison of our results with statistical coupling analysis (SCA) provides further support. The methodology proposed here is general and can be applied to similar problems of interest.

Item Type: Journal Article
Additional Information: Copyright for this article belongs to PUBLIC LIBRARY SCIENCE, SAN FRANCISCO, USA
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Depositing User: Francis Jayakanth
Date Deposited: 24 Jan 2013 05:25
Last Modified: 24 Jan 2013 05:25
URI: http://eprints.iisc.ac.in/id/eprint/45664

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