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== | ==Structure of an M.tuberculosis LEH-like epoxide hydrolase== | ||
<StructureSection load='2bng' size='340' side='right'caption='[[2bng]], [[Resolution|resolution]] 2.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2bng]] is a 3 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=2BNG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BNG 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]] 2.5Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=2bng FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bng OCA], [https://pdbe.org/2bng PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bng RCSB], [https://www.ebi.ac.uk/pdbsum/2bng PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bng ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/EPHG_MYCTU EPHG_MYCTU] Epoxide hydrolase capable of hydrolyzing long or bulky lipophilic epoxides such as 9,10-epoxystearic acid and cholesterol 5,6-oxide in vitro. The physiological substrates have yet to be identified, but could be fatty acid or steroid derivatives.<ref>PMID:16051262</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/bn/2bng_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2bng ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Epoxide hydrolases are vital to many organisms by virtue of their roles in detoxification, metabolism and processing of signaling molecules. The Mycobacterium tuberculosis genome encodes an unusually large number of epoxide hydrolases, suggesting that they might be of particular importance to these bacteria. We report here the first structure of an epoxide hydrolase from M.tuberculosis, solved to a resolution of 2.5 A using single-wavelength anomalous dispersion (SAD) from a selenomethionine-substituted protein. The enzyme features a deep active-site pocket created by the packing of three helices onto a curved six-stranded beta-sheet. This structure is similar to a previously described limonene-1,2-epoxide hydrolase from Rhodococcus erythropolis and unlike the alpha/beta-hydrolase fold typical of mammalian epoxide hydrolases (EH). A number of changes in the mycobacterial enzyme create a wider and deeper substrate-binding pocket than is found in its Rhodococcus homologue. Interestingly, each structure contains a different type of endogenous ligand of unknown origin bound in its active site. As a consequence of its wider substrate-binding pocket, the mycobacterial EH is capable of hydrolyzing long or bulky lipophilic epoxides such as 10,11-epoxystearic acid and cholesterol 5,6-oxide at appreciable rates, suggesting that similar compound(s) will serve as its physiological substrate(s). | Epoxide hydrolases are vital to many organisms by virtue of their roles in detoxification, metabolism and processing of signaling molecules. The Mycobacterium tuberculosis genome encodes an unusually large number of epoxide hydrolases, suggesting that they might be of particular importance to these bacteria. We report here the first structure of an epoxide hydrolase from M.tuberculosis, solved to a resolution of 2.5 A using single-wavelength anomalous dispersion (SAD) from a selenomethionine-substituted protein. The enzyme features a deep active-site pocket created by the packing of three helices onto a curved six-stranded beta-sheet. This structure is similar to a previously described limonene-1,2-epoxide hydrolase from Rhodococcus erythropolis and unlike the alpha/beta-hydrolase fold typical of mammalian epoxide hydrolases (EH). A number of changes in the mycobacterial enzyme create a wider and deeper substrate-binding pocket than is found in its Rhodococcus homologue. Interestingly, each structure contains a different type of endogenous ligand of unknown origin bound in its active site. As a consequence of its wider substrate-binding pocket, the mycobacterial EH is capable of hydrolyzing long or bulky lipophilic epoxides such as 10,11-epoxystearic acid and cholesterol 5,6-oxide at appreciable rates, suggesting that similar compound(s) will serve as its physiological substrate(s). | ||
Structure of an atypical epoxide hydrolase from Mycobacterium tuberculosis gives insights into its function.,Johansson P, Unge T, Cronin A, Arand M, Bergfors T, Jones TA, Mowbray SL J Mol Biol. 2005 Sep 2;351(5):1048-56. PMID:16051262<ref>PMID:16051262</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
[[Category: | <div class="pdbe-citations 2bng" style="background-color:#fffaf0;"></div> | ||
[[Category: Mycobacterium tuberculosis | == References == | ||
<references/> | |||
[[Category: Arand | __TOC__ | ||
[[Category: Bergfors | </StructureSection> | ||
[[Category: Johansson | [[Category: Large Structures]] | ||
[[Category: Jones | [[Category: Mycobacterium tuberculosis H37Rv]] | ||
[[Category: Mowbray | [[Category: Arand M]] | ||
[[Category: Bergfors T]] | |||
[[Category: Unge | [[Category: Johansson P]] | ||
[[Category: Jones TA]] | |||
[[Category: Mowbray SL]] | |||
[[Category: Unge T]] | |||
Latest revision as of 12:01, 6 November 2024
Structure of an M.tuberculosis LEH-like epoxide hydrolaseStructure of an M.tuberculosis LEH-like epoxide hydrolase
Structural highlights
FunctionEPHG_MYCTU Epoxide hydrolase capable of hydrolyzing long or bulky lipophilic epoxides such as 9,10-epoxystearic acid and cholesterol 5,6-oxide in vitro. The physiological substrates have yet to be identified, but could be fatty acid or steroid derivatives.[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 PubMedEpoxide hydrolases are vital to many organisms by virtue of their roles in detoxification, metabolism and processing of signaling molecules. The Mycobacterium tuberculosis genome encodes an unusually large number of epoxide hydrolases, suggesting that they might be of particular importance to these bacteria. We report here the first structure of an epoxide hydrolase from M.tuberculosis, solved to a resolution of 2.5 A using single-wavelength anomalous dispersion (SAD) from a selenomethionine-substituted protein. The enzyme features a deep active-site pocket created by the packing of three helices onto a curved six-stranded beta-sheet. This structure is similar to a previously described limonene-1,2-epoxide hydrolase from Rhodococcus erythropolis and unlike the alpha/beta-hydrolase fold typical of mammalian epoxide hydrolases (EH). A number of changes in the mycobacterial enzyme create a wider and deeper substrate-binding pocket than is found in its Rhodococcus homologue. Interestingly, each structure contains a different type of endogenous ligand of unknown origin bound in its active site. As a consequence of its wider substrate-binding pocket, the mycobacterial EH is capable of hydrolyzing long or bulky lipophilic epoxides such as 10,11-epoxystearic acid and cholesterol 5,6-oxide at appreciable rates, suggesting that similar compound(s) will serve as its physiological substrate(s). Structure of an atypical epoxide hydrolase from Mycobacterium tuberculosis gives insights into its function.,Johansson P, Unge T, Cronin A, Arand M, Bergfors T, Jones TA, Mowbray SL J Mol Biol. 2005 Sep 2;351(5):1048-56. PMID:16051262[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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