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The structure of a pH-sensing mycobacterial adenylyl cyclase holoenzyme

The structure of a pH-sensing mycobacterial adenylyl cyclase holoenzyme
The structure of a pH-sensing mycobacterial adenylyl cyclase holoenzyme
Class III adenylyl cyclases contain catalytic and regulatory domains, yet structural insight into their interactions is missing. We show that the mycobacterial adenylyl cyclase Rv1264 is rendered a pH sensor by its N-terminal domain. In the structure of the inhibited state, catalytic and regulatory domains share a large interface involving catalytic residues. In the structure of the active state, the two catalytic domains rotate by 55 degrees to form two catalytic sites at their interface. Two alpha helices serve as molecular switches. Mutagenesis is consistent with a regulatory role of the structural transition, and we suggest that the transition is regulated by pH.
0036-8075
1020-1023
Tews, Ivo
9117fc5e-d01c-4f8d-a734-5b14d3eee8dd
Findeisen, Felix
c6f157a7-30ed-4400-bf15-c6603024aaed
Sinning, Irmgard
fbc3f199-8a3b-47a6-9ee7-00bfc472e079
Schultz, Anita
88dff698-b107-4aa0-9476-cb88d6f26015
Schultz, Joachim E
7e091719-97bf-4742-a0c2-4b8213642b05
Linder, Jürgen U
3baa084f-7034-4d06-990f-1b2c5cb77612
Tews, Ivo
9117fc5e-d01c-4f8d-a734-5b14d3eee8dd
Findeisen, Felix
c6f157a7-30ed-4400-bf15-c6603024aaed
Sinning, Irmgard
fbc3f199-8a3b-47a6-9ee7-00bfc472e079
Schultz, Anita
88dff698-b107-4aa0-9476-cb88d6f26015
Schultz, Joachim E
7e091719-97bf-4742-a0c2-4b8213642b05
Linder, Jürgen U
3baa084f-7034-4d06-990f-1b2c5cb77612

Tews, Ivo, Findeisen, Felix, Sinning, Irmgard, Schultz, Anita, Schultz, Joachim E and Linder, Jürgen U (2005) The structure of a pH-sensing mycobacterial adenylyl cyclase holoenzyme. Science, 308 (5724), 1020-1023. (doi:10.1126/science.1107642). (PMID:15890882)

Record type: Article

Abstract

Class III adenylyl cyclases contain catalytic and regulatory domains, yet structural insight into their interactions is missing. We show that the mycobacterial adenylyl cyclase Rv1264 is rendered a pH sensor by its N-terminal domain. In the structure of the inhibited state, catalytic and regulatory domains share a large interface involving catalytic residues. In the structure of the active state, the two catalytic domains rotate by 55 degrees to form two catalytic sites at their interface. Two alpha helices serve as molecular switches. Mutagenesis is consistent with a regulatory role of the structural transition, and we suggest that the transition is regulated by pH.

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More information

Published date: 13 May 2005
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 200655
URI: http://eprints.soton.ac.uk/id/eprint/200655
ISSN: 0036-8075
PURE UUID: 25ae158b-11cf-417f-aad0-fe9a26096dfc
ORCID for Ivo Tews: ORCID iD orcid.org/0000-0002-4704-1139

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Date deposited: 01 Nov 2011 15:44
Last modified: 03 Dec 2019 01:41

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