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A structural basis for the role of nucleotide specifying residues in regulating the Rv1625c adenylyl cyclase oligomerization of the from M-tuberculosis

Ketkar, AD and Shenoy, AR and Ramagopal, UA and Visweswariah, Sandhya S and Suguna, K (2006) A structural basis for the role of nucleotide specifying residues in regulating the Rv1625c adenylyl cyclase oligomerization of the from M-tuberculosis. In: Journal of Molecular Biology , 356 (4). pp. 904-916.

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Official URL: http://dx.doi.org/10.1016/j.jmb.2005.12.017

Abstract

The Rv1625c Class III adenylyl cyclase from Mycobacterium tuberculosis is a homodimeric enzyme with two catalytic centers at the dimer interface, and shows sequence similarity with the mammalian adenylyl and guanylyl cyclases. Mutation of the substrate-specifying residues in the catalytic domain of Rv1625c, either independently or together, to those present in guanylyl cyclases not only failed to confer guanylyl cyclase activity to the protein, but also severely abrogated the adenylyl cyclase activity of the enzyme. Biochemical analysis revealed alterations in the behavior of the mutants on ion-exchange chromatography, indicating differences in the surface-exposed charge upon mutation of substrate-specifying residues. The mutant proteins showed alterations in oligomeric status as compared to the wild-type enzyme, and differing abilities to heterodimerize with the wild-type protein. The crystal structure of a mutant has been solved to a resolution of 2.7 angstrom. On the basis of the structure, and additional biochemical studies, we provide possible reasons for the altered properties of the mutant proteins, as well as highlight unique structural features of the Rv1625c adenylyl cyclase. (c) 2005 Elsevier Ltd. All rights reserved.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to Elsevier Science.
Keywords: Nucleotide cyclase; Mycobacterium tuberculosis; cAMP; crystal structure.
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Division of Biological Sciences > Molecular Reproduction, Development & Genetics (formed by the merger of DBGL and CRBME)
Date Deposited: 29 Oct 2010 07:05
Last Modified: 29 Oct 2010 07:05
URI: http://eprints.iisc.ernet.in/id/eprint/32805

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