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Crystal structure of an adenylyl cyclase Ma1120 from Mycobacterium avium in complex with ATP and calcium ionCrystal structure of an adenylyl cyclase Ma1120 from Mycobacterium avium in complex with ATP and calcium ion
Structural highlights
FunctionPublication Abstract from PubMedThe two second messengers in signaling, cyclic AMP and cyclic GMP, are produced by adenylyl and guanylyl cyclases, respectively. Recognition and discrimination of the substrates ATP and GTP by the nucleotidyl cyclases is vital in these reactions. Various apo, substrate or inhibitor bound forms of adenylyl cyclase (AC) structures from transmembrane and soluble ACs have revealed the catalytic mechanism of ATP cyclization reaction. Previously reported structures of guanylyl cyclases represent ligand-free forms and inactive open states of the enzymes and thus do not provide information regarding the exact mode of substrate binding. The structures we present here of the cyclase homology domain of a class III AC from Mycobacterium avium (Ma1120) and its mutant in complex with ATP and GTP in the presence of calcium ion, provide the structural basis for substrate selection by the nucleotidyl cyclases at the atomic level. Precise nature of the enzyme-substrate interactions, novel modes of substrate binding and the ability of the binding pocket to accommodate diverse conformations of the substrates have been revealed by the present crystallographic analysis. This is the first report to provide structures of both the nucleotide substrates bound to a nucleotidyl cyclase. This article is protected by copyright. All rights reserved. Substrate specificity determinants of class III nucleotidyl cyclases.,Bharambe NG, Barathy DV, Syed W, Visweswariah SS, Colavarsigmao M, Misquith S, Suguna K FEBS J. 2016 Aug 20. doi: 10.1111/febs.13837. PMID:27542992[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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