Structural highlights
Publication Abstract from PubMedProtein function often depends on the exchange between conformational substates. Allosteric ligand binding or distal mutations can stabilize specific active-site conformations and consequently alter protein function. Observing alternative conformations at low levels of electron density, in addition to comparison of independently determined X-ray crystal structures, can provide mechanistic insights into conformational dynamics. Here we report a new algorithm, CONTACT, that identifies contact networks of conformationally heterogeneous residues directly from high-resolution X-ray crystallography data. Contact networks determined for Escherichia coli dihydrofolate reductase (ecDHFR) predict the observed long-range pattern of NMR chemical shift perturbations of an allosteric mutation. A comparison of contact networks in wild-type and mutant ecDHFR suggests that mutations that alter optimized contact networks of coordinated motions can impair catalytic function. CONTACT-guided mutagenesis can exploit the structure-dynamics-function relationship in protein engineering and design. Automated identification of functional dynamic contact networks from X-ray crystallography.,van den Bedem H, Bhabha G, Yang K, Wright PE, Fraser JS Nat Methods. 2013 Aug 4. doi: 10.1038/nmeth.2592. PMID:23913260[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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