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Fatty acid regulation of adenylyl cyclase Rv2212 from Mycobacterium tuberculosis H37Rv

Fatty acid regulation of adenylyl cyclase Rv2212 from Mycobacterium tuberculosis H37Rv
Fatty acid regulation of adenylyl cyclase Rv2212 from Mycobacterium tuberculosis H37Rv
Adenylyl cyclase Rv2212 from Mycobacterium tuberculosis has a domain composition identical to the pH-sensing isoform Rv1264, an N-terminal regulatory domain and a C-terminal catalytic domain. The maximal velocity of Rv2212 was the highest of all 10 mycobacterial cyclases investigated to date (3.9 micromol cAMP.mg(-1).min(-1)), whereas ATP substrate affinity was low (SC(50) = 2.1 mm ATP). Guanylyl cyclase side activity was absent. The activities and kinetics of the holoenzyme and of the catalytic domain alone were similar, i.e. in distinct contrast to the Rv1264 adenylyl cyclase, in which the N-terminal domain is autoinhibitory. Unsaturated fatty acids strongly stimulated Rv2212 activity by increasing substrate affinity. In addition, fatty acids greatly enhanced the pH sensitivity of the holoenzyme, thus converting Rv2212 to a pH sensor adenylyl cyclase. Fatty acid binding to Rv2212 was modelled by homology to a recent structure of the N-terminal domain of Rv1264, in which a fatty acid-binding pocket is defined. Rv2212 appears to integrate three cellular parameters: ATP concentration, presence of unsaturated fatty acids, and pH. These regulatory properties open the possibility that novel modes of cAMP-mediated signal transduction exist in the pathogen.
1742-464X
4219-4228
Abdel Motaal, Amira
26a96254-c70e-4a37-ba13-781afc6f485d
Tews, Ivo
9117fc5e-d01c-4f8d-a734-5b14d3eee8dd
Schultz, Joachim E
7e091719-97bf-4742-a0c2-4b8213642b05
Linder, Jürgen U
3baa084f-7034-4d06-990f-1b2c5cb77612
Abdel Motaal, Amira
26a96254-c70e-4a37-ba13-781afc6f485d
Tews, Ivo
9117fc5e-d01c-4f8d-a734-5b14d3eee8dd
Schultz, Joachim E
7e091719-97bf-4742-a0c2-4b8213642b05
Linder, Jürgen U
3baa084f-7034-4d06-990f-1b2c5cb77612

Abdel Motaal, Amira, Tews, Ivo, Schultz, Joachim E and Linder, Jürgen U (2006) Fatty acid regulation of adenylyl cyclase Rv2212 from Mycobacterium tuberculosis H37Rv. Febs Journal, 273 (18), 4219-4228. (doi:10.1111/j.1742-4658.2006.05420.x). (PMID:16925585)

Record type: Article

Abstract

Adenylyl cyclase Rv2212 from Mycobacterium tuberculosis has a domain composition identical to the pH-sensing isoform Rv1264, an N-terminal regulatory domain and a C-terminal catalytic domain. The maximal velocity of Rv2212 was the highest of all 10 mycobacterial cyclases investigated to date (3.9 micromol cAMP.mg(-1).min(-1)), whereas ATP substrate affinity was low (SC(50) = 2.1 mm ATP). Guanylyl cyclase side activity was absent. The activities and kinetics of the holoenzyme and of the catalytic domain alone were similar, i.e. in distinct contrast to the Rv1264 adenylyl cyclase, in which the N-terminal domain is autoinhibitory. Unsaturated fatty acids strongly stimulated Rv2212 activity by increasing substrate affinity. In addition, fatty acids greatly enhanced the pH sensitivity of the holoenzyme, thus converting Rv2212 to a pH sensor adenylyl cyclase. Fatty acid binding to Rv2212 was modelled by homology to a recent structure of the N-terminal domain of Rv1264, in which a fatty acid-binding pocket is defined. Rv2212 appears to integrate three cellular parameters: ATP concentration, presence of unsaturated fatty acids, and pH. These regulatory properties open the possibility that novel modes of cAMP-mediated signal transduction exist in the pathogen.

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Published date: September 2006
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 200621
URI: https://eprints.soton.ac.uk/id/eprint/200621
ISSN: 1742-464X
PURE UUID: d7f63a5d-b4f3-47a5-9d7a-a4ae250ea6c1
ORCID for Ivo Tews: ORCID iD orcid.org/0000-0002-4704-1139

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Date deposited: 01 Nov 2011 14:41
Last modified: 06 Jun 2018 12:33

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