2a5v
From Proteopedia
(New page: 200px<br /><applet load="2a5v" size="350" color="white" frame="true" align="right" spinBox="true" caption="2a5v, resolution 2.20Å" /> '''Crystal structure of...) |
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==Overview== | ==Overview== | ||
| - | Carbonic anhydrases catalyze the reversible hydration of carbon dioxide to | + | Carbonic anhydrases catalyze the reversible hydration of carbon dioxide to form bicarbonate, a reaction required for many functions, including carbon assimilation and pH homeostasis. Carbonic anhydrases are divided into at least three classes and are believed to share a zinc-hydroxide mechanism for carbon dioxide hydration. beta-carbonic anhydrases are broadly spread among the domains of life, and existing structures from different organisms show two distinct active site setups, one with three protein coordinations to the zinc (accessible) and the other with four (blocked). The latter is believed to be inconsistent with the zinc-hydroxide mechanism. The Mycobacterium tuberculosis Rv3588c gene, shown to be required for in vivo growth of the pathogen, encodes a beta-carbonic anhydrase with a steep pH dependence of its activity, being active at pH 8.4 but not at pH 7.5. We have recently solved the structure of this protein, which was a dimeric protein with a blocked active site. Here we present the structure of the thiocyanate complexed protein in a different crystal form. The protein now forms distinct tetramers and shows large structural changes, including a carboxylate shift yielding the accessible active site. This structure demonstrated for the first time that a beta-carbonic anhydrase can switch between the two states. A pH-dependent dimer to tetramer equilibrium was also demonstrated by dynamic light scattering measurements. The data presented here, therefore, suggest a carboxylate shift on/off switch for the enzyme, which may, in turn, be controlled by a dimer-to-tetramer equilibrium. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Bergfors, T.]] | [[Category: Bergfors, T.]] | ||
| - | [[Category: Covarrubias, A | + | [[Category: Covarrubias, A S.]] |
[[Category: Hogbom, M.]] | [[Category: Hogbom, M.]] | ||
| - | [[Category: Jones, T | + | [[Category: Jones, T A.]] |
[[Category: SCN]] | [[Category: SCN]] | ||
[[Category: ZN]] | [[Category: ZN]] | ||
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[[Category: zinc]] | [[Category: zinc]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:23:53 2008'' |
Revision as of 14:23, 21 February 2008
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Crystal structure of M. tuberculosis beta carbonic anhydrase, Rv3588c, tetrameric form
Overview
Carbonic anhydrases catalyze the reversible hydration of carbon dioxide to form bicarbonate, a reaction required for many functions, including carbon assimilation and pH homeostasis. Carbonic anhydrases are divided into at least three classes and are believed to share a zinc-hydroxide mechanism for carbon dioxide hydration. beta-carbonic anhydrases are broadly spread among the domains of life, and existing structures from different organisms show two distinct active site setups, one with three protein coordinations to the zinc (accessible) and the other with four (blocked). The latter is believed to be inconsistent with the zinc-hydroxide mechanism. The Mycobacterium tuberculosis Rv3588c gene, shown to be required for in vivo growth of the pathogen, encodes a beta-carbonic anhydrase with a steep pH dependence of its activity, being active at pH 8.4 but not at pH 7.5. We have recently solved the structure of this protein, which was a dimeric protein with a blocked active site. Here we present the structure of the thiocyanate complexed protein in a different crystal form. The protein now forms distinct tetramers and shows large structural changes, including a carboxylate shift yielding the accessible active site. This structure demonstrated for the first time that a beta-carbonic anhydrase can switch between the two states. A pH-dependent dimer to tetramer equilibrium was also demonstrated by dynamic light scattering measurements. The data presented here, therefore, suggest a carboxylate shift on/off switch for the enzyme, which may, in turn, be controlled by a dimer-to-tetramer equilibrium.
About this Structure
2A5V is a Single protein structure of sequence from Mycobacterium tuberculosis h37rv with and as ligands. Active as Carbonate dehydratase, with EC number 4.2.1.1 Full crystallographic information is available from OCA.
Reference
Structural mechanics of the pH-dependent activity of beta-carbonic anhydrase from Mycobacterium tuberculosis., Covarrubias AS, Bergfors T, Jones TA, Hogbom M, J Biol Chem. 2006 Feb 24;281(8):4993-9. Epub 2005 Dec 1. PMID:16321983
Page seeded by OCA on Thu Feb 21 16:23:53 2008
