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| - | [[Image:2ev4.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_2ev4| PDB=2ev4 | SCENE= }} | | {{STRUCTURE_2ev4| PDB=2ev4 | SCENE= }} |
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| - | '''Structure of Rv1264N, the regulatory domain of the mycobacterial adenylyl cylcase Rv1264, with a salt precipitant'''
| + | ===Structure of Rv1264N, the regulatory domain of the mycobacterial adenylyl cylcase Rv1264, with a salt precipitant=== |
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| - | ==Overview==
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| - | The universal secondary messenger cAMP is produced by adenylyl cyclases (ACs). Most bacterial and all eukaryotic ACs belong to class III of six divergent classes. A class III characteristic is formation of the catalytic pocket at a dimer interface and the presence of additional regulatory domains. Mycobacterium tuberculosis possesses 15 class III ACs, including Rv1264, which is activated at acidic pH due to pH-dependent structural transitions of the Rv1264 dimer. It has been shown by X-ray crystallography that the N-terminal regulatory and C-terminal catalytic domains of Rv1264 interact in completely different ways in the active and inhibited states. Here, we report an in-depth structural and functional analysis of the regulatory domain of Rv1264. The 1.6 A resolution crystal structure shows the protein in a tight, disk-shaped dimer, formed around a helical bundle, and involving a protein chain crossover. To understand pH regulation, we determined structures at acidic and basic pH values and employed structure-based mutagenesis in the holoenzyme to elucidate regulation using an AC activity assay. It has been shown that regulatory and catalytic domains must be linked in a single protein chain. The new studies demonstrate that the length of the linker segment is decisive for regulation. Several amino acids on the surface of the regulatory domain, when exchanged, altered the pH-dependence of AC activity. However, these residues are not conserved amongst a number of related ACs. The closely related mycobacterial Rv2212, but not Rv1264, is strongly activated by the addition of fatty acids. The structure resolved the presence of a deeply embedded fatty acid, characterised as oleic acid by mass spectrometry, which may serve as a hinge. From these data, we conclude that the regulatory domain is a structural scaffold used for distinct regulatory purposes.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_17482646}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 17482646 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_17482646}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Oleic acid]] | | [[Category: Oleic acid]] |
| | [[Category: Regulatory domain of adenylyl cyclase]] | | [[Category: Regulatory domain of adenylyl cyclase]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed May 28 09:29:49 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 21:14:13 2008'' |
Revision as of 18:14, 27 July 2008
Template:STRUCTURE 2ev4
Structure of Rv1264N, the regulatory domain of the mycobacterial adenylyl cylcase Rv1264, with a salt precipitant
Template:ABSTRACT PUBMED 17482646
About this Structure
2EV4 is a Single protein structure of sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA.
Reference
The structure of the regulatory domain of the adenylyl cyclase Rv1264 from Mycobacterium tuberculosis with bound oleic acid., Findeisen F, Linder JU, Schultz A, Schultz JE, Brugger B, Wieland F, Sinning I, Tews I, J Mol Biol. 2007 Jun 22;369(5):1282-95. Epub 2007 Apr 12. PMID:17482646
Page seeded by OCA on Sun Jul 27 21:14:13 2008
