1l9d: Difference between revisions
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< | ==Role of Histidine 269 in Catalysis by Monomeric Sarcosine Oxidase== | ||
<StructureSection load='1l9d' size='340' side='right'caption='[[1l9d]], [[Resolution|resolution]] 1.95Å' scene=''> | |||
You may | == Structural highlights == | ||
or the | <table><tr><td colspan='2'>[[1l9d]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_sp._B-0618 Bacillus sp. B-0618]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L9D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1L9D 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]] 1.95Å</td></tr> | |||
-- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=PYC:PYRROLE-2-CARBOXYLATE'>PYC</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=1l9d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l9d OCA], [https://pdbe.org/1l9d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1l9d RCSB], [https://www.ebi.ac.uk/pdbsum/1l9d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1l9d ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/MSOX_BACB0 MSOX_BACB0] Catalyzes the oxidative demethylation of sarcosine. Can also oxidize other secondary amino acids such as N-methyl-L-alanine.[HAMAP-Rule:MF_00516] | |||
== 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/l9/1l9d_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=1l9d ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Conservative mutation of His269 (to Asn, Ala, or Gln) does not-significantly affect the expression of monomeric sarcosine oxidase (MSOX), covalent flavinylation, the physicochemical properties of bound FAD, or the overall protein structure. Turnover with sarcosine and the limiting rate of the reductive half-reaction with L-proline at pH 8.0 are, however, nearly 2 orders of magnitude slower than that with with wild-type MSOX. The crystal structure of the His269Asn complex with pyrrole-2-carboxylate shows that the pyrrole ring of the inhibitor is displaced as compared with wild-type MSOX. The His269 mutants all form charge-transfer complexes with pyrrole-2-carboxylate or methylthioacetate, but the charge-transfer bands are shifted to shorter wavelengths (higher energy) as compared with wild-type MSOX. Both wild-type MSOX and the His269Asn mutant bind the zwitterionic form of L-proline. The E(ox).L-proline complex formed with the His269Asn mutant or wild-type MSOX contains an ionizable group (pK(a) = 8.0) that is required for conversion of the zwitterionic L-proline to the reactive anionic form, indicating that His269 is not the active-site base. We propose that the change in ligand orientation observed upon mutation of His269 results in a less than optimal overlap of the highest occupied orbital of the ligand with the lowest unoccupied orbital of the flavin. The postulated effect on orbital overlap may account for the increased energy of charge-transfer bands and the slower rates of electron transfer observed for mutant enzyme complexes with charge-transfer ligands and substrates, respectively. | |||
Monomeric sarcosine oxidase: role of histidine 269 in catalysis.,Zhao G, Song H, Chen ZW, Mathews FS, Jorns MS Biochemistry. 2002 Aug 6;41(31):9751-64. PMID:12146941<ref>PMID:12146941</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1l9d" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Sarcosine oxidase|Sarcosine oxidase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Bacillus sp. B-0618]] | ||
[[Category: Large Structures]] | |||
[[Category: Chen Z-w]] | |||
== | [[Category: Jorns MS]] | ||
[[Category: Mathews FS]] | |||
[[Category: Bacillus sp.]] | [[Category: Song H]] | ||
[[Category: | [[Category: Zhao G]] | ||
[[Category: Chen | |||
[[Category: Jorns | |||
[[Category: Mathews | |||
[[Category: Song | |||
[[Category: Zhao | |||
Latest revision as of 03:12, 21 November 2024
Role of Histidine 269 in Catalysis by Monomeric Sarcosine OxidaseRole of Histidine 269 in Catalysis by Monomeric Sarcosine Oxidase
Structural highlights
FunctionMSOX_BACB0 Catalyzes the oxidative demethylation of sarcosine. Can also oxidize other secondary amino acids such as N-methyl-L-alanine.[HAMAP-Rule:MF_00516] 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 PubMedConservative mutation of His269 (to Asn, Ala, or Gln) does not-significantly affect the expression of monomeric sarcosine oxidase (MSOX), covalent flavinylation, the physicochemical properties of bound FAD, or the overall protein structure. Turnover with sarcosine and the limiting rate of the reductive half-reaction with L-proline at pH 8.0 are, however, nearly 2 orders of magnitude slower than that with with wild-type MSOX. The crystal structure of the His269Asn complex with pyrrole-2-carboxylate shows that the pyrrole ring of the inhibitor is displaced as compared with wild-type MSOX. The His269 mutants all form charge-transfer complexes with pyrrole-2-carboxylate or methylthioacetate, but the charge-transfer bands are shifted to shorter wavelengths (higher energy) as compared with wild-type MSOX. Both wild-type MSOX and the His269Asn mutant bind the zwitterionic form of L-proline. The E(ox).L-proline complex formed with the His269Asn mutant or wild-type MSOX contains an ionizable group (pK(a) = 8.0) that is required for conversion of the zwitterionic L-proline to the reactive anionic form, indicating that His269 is not the active-site base. We propose that the change in ligand orientation observed upon mutation of His269 results in a less than optimal overlap of the highest occupied orbital of the ligand with the lowest unoccupied orbital of the flavin. The postulated effect on orbital overlap may account for the increased energy of charge-transfer bands and the slower rates of electron transfer observed for mutant enzyme complexes with charge-transfer ligands and substrates, respectively. Monomeric sarcosine oxidase: role of histidine 269 in catalysis.,Zhao G, Song H, Chen ZW, Mathews FS, Jorns MS Biochemistry. 2002 Aug 6;41(31):9751-64. PMID:12146941[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
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