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== | ==X-ray crystal structure of HsaD from Mycobacterium tuberculosis== | ||
Tuberculosis is a major cause of death worldwide. Understanding of the | <StructureSection load='2vf2' size='340' side='right'caption='[[2vf2]], [[Resolution|resolution]] 2.35Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2vf2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VF2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VF2 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.35Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2vf2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vf2 OCA], [https://pdbe.org/2vf2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vf2 RCSB], [https://www.ebi.ac.uk/pdbsum/2vf2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vf2 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/HSAD_MYCTU HSAD_MYCTU] Catalyzes the hydrolysis of a carbon-carbon bond in 4,5: 9,10-diseco-3-hydroxy-5,9,17-trioxoandrosta-1(10),2-diene-4-oate (4,9-DSHA) to yield 9,17-dioxo-1,2,3,4,10,19-hexanorandrostan-5-oate (DOHNAA) and 2-hydroxy-hexa-2,4-dienoate (HHD). Is also able to catalyze the hydrolysis of 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid (HOPDA) and the synthetic analog 8-(2-chlorophenyl)-2-hydroxy-5-methyl-6-oxoocta-2,4-dienoic acid (HOPODA).<ref>PMID:19875455</ref> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vf/2vf2_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2vf2 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Tuberculosis is a major cause of death worldwide. Understanding of the pathogenicity of Mycobacterium tuberculosis has been advanced by gene analysis and has led to the identification of genes that are important for intracellular survival in macrophages. One of these genes encodes HsaD, a meta-cleavage product (MCP) hydrolase that catalyzes the hydrolytic cleavage of a carbon-carbon bond in cholesterol metabolism. This paper describes the production of HsaD as a recombinant protein and, following crystallization, the determination of its three-dimensional structure to 2.35 A resolution by X-ray crystallography at the Diamond Light Source in Oxfordshire, England. To the authors' knowledge, this study constitutes the first report of a structure determined at the new synchrotron facility. The volume of the active-site cleft of the HsaD enzyme is more than double the corresponding active-site volumes of related MCP hydrolases involved in the catabolism of aromatic compounds, consistent with the specificity of HsaD for steroids such as cholesterol. Knowledge of the structure of the enzyme facilitates the design of inhibitors. | |||
Structure of HsaD, a steroid-degrading hydrolase, from Mycobacterium tuberculosis.,Lack N, Lowe ED, Liu J, Eltis LD, Noble ME, Sim E, Westwood IM Acta Crystallogr Sect F Struct Biol Cryst Commun. 2008 Jan 1;64(Pt 1):2-7., Epub 2007 Dec 20. PMID:18097091<ref>PMID:18097091</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
[[Category: | <div class="pdbe-citations 2vf2" style="background-color:#fffaf0;"></div> | ||
[[Category: Mycobacterium tuberculosis | == References == | ||
<references/> | |||
[[Category: Eltis | __TOC__ | ||
[[Category: Lack | </StructureSection> | ||
[[Category: Liu | [[Category: Large Structures]] | ||
[[Category: Lowe | [[Category: Mycobacterium tuberculosis H37Rv]] | ||
[[Category: Noble | [[Category: Eltis LD]] | ||
[[Category: Sim | [[Category: Lack N]] | ||
[[Category: Westwood | [[Category: Liu J]] | ||
[[Category: Lowe ED]] | |||
[[Category: Noble MEM]] | |||
[[Category: Sim E]] | |||
[[Category: Westwood IM]] | |||
Latest revision as of 18:18, 13 December 2023
X-ray crystal structure of HsaD from Mycobacterium tuberculosisX-ray crystal structure of HsaD from Mycobacterium tuberculosis
Structural highlights
FunctionHSAD_MYCTU Catalyzes the hydrolysis of a carbon-carbon bond in 4,5: 9,10-diseco-3-hydroxy-5,9,17-trioxoandrosta-1(10),2-diene-4-oate (4,9-DSHA) to yield 9,17-dioxo-1,2,3,4,10,19-hexanorandrostan-5-oate (DOHNAA) and 2-hydroxy-hexa-2,4-dienoate (HHD). Is also able to catalyze the hydrolysis of 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid (HOPDA) and the synthetic analog 8-(2-chlorophenyl)-2-hydroxy-5-methyl-6-oxoocta-2,4-dienoic acid (HOPODA).[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedTuberculosis is a major cause of death worldwide. Understanding of the pathogenicity of Mycobacterium tuberculosis has been advanced by gene analysis and has led to the identification of genes that are important for intracellular survival in macrophages. One of these genes encodes HsaD, a meta-cleavage product (MCP) hydrolase that catalyzes the hydrolytic cleavage of a carbon-carbon bond in cholesterol metabolism. This paper describes the production of HsaD as a recombinant protein and, following crystallization, the determination of its three-dimensional structure to 2.35 A resolution by X-ray crystallography at the Diamond Light Source in Oxfordshire, England. To the authors' knowledge, this study constitutes the first report of a structure determined at the new synchrotron facility. The volume of the active-site cleft of the HsaD enzyme is more than double the corresponding active-site volumes of related MCP hydrolases involved in the catabolism of aromatic compounds, consistent with the specificity of HsaD for steroids such as cholesterol. Knowledge of the structure of the enzyme facilitates the design of inhibitors. Structure of HsaD, a steroid-degrading hydrolase, from Mycobacterium tuberculosis.,Lack N, Lowe ED, Liu J, Eltis LD, Noble ME, Sim E, Westwood IM Acta Crystallogr Sect F Struct Biol Cryst Commun. 2008 Jan 1;64(Pt 1):2-7., Epub 2007 Dec 20. PMID:18097091[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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