5D0G

Crystal structure of triple mutant (KDA to EGY) of adenylyl cyclase Ma1120 from Mycobacterium avium in complex with GTP and calcium ion

Summary for 5D0G

• Entry DOI: 10.2210/pdb5d0g/pdb
• Related: 5D0E 5D0H 5D15
• Descriptor: Cyclase, GUANOSINE-5'-TRIPHOSPHATE, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: adenylyl cyclase, gtp, lyase
• Biological source: Mycobacterium avium subsp. avium 10-9275
• Total number of polymer chains: 2
• Total formula weight: 40369.19

Authors

Bharambe, N.G.,Suguna, K. (deposition date: 2015-08-03, release date: 2016-08-10, Last modification date: 2023-11-08)

Primary citation

Bharambe, N.G.,Barathy, D.V.,Syed, W.,Visweswariah, S.S.,Cola sigmaf o, M.,Misquith, S.,Suguna, K.
Substrate specificity determinants of class III nucleotidyl cyclases
Febs J., 283:3723-3738, 2016

PubMed Abstract: The two second messengers in signalling, 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 are 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.

PubMed: 27542992
DOI: 10.1111/febs.13837

Experimental method

X-RAY DIFFRACTION (1.6 Å)