7cdl: Difference between revisions
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==== | ==holo-methanol dehydrogenase (MDH) with Cys131-Cys132 reduced from Methylococcus capsulatus (Bath)== | ||
<StructureSection load='7cdl' size='340' side='right'caption='[[7cdl]]' scene=''> | <StructureSection load='7cdl' size='340' side='right'caption='[[7cdl]], [[Resolution|resolution]] 1.85Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7cdl]] is a 16 chain structure with sequence from [https://en.wikipedia.org/wiki/Methylococcus_capsulatus_str._Bath Methylococcus capsulatus str. Bath]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CDL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CDL FirstGlance]. <br> | ||
</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=7cdl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cdl OCA], [https://pdbe.org/7cdl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cdl RCSB], [https://www.ebi.ac.uk/pdbsum/7cdl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cdl ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85Å</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=PQQ:PYRROLOQUINOLINE+QUINONE'>PQQ</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=7cdl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cdl OCA], [https://pdbe.org/7cdl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cdl RCSB], [https://www.ebi.ac.uk/pdbsum/7cdl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cdl ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/Q60AR6_METCA Q60AR6_METCA] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The active site of methanol dehydrogenase (MDH) contains a rare disulfide bridge between adjacent cysteine residues. As a vicinal disulfide, the structure is highly strained, suggesting it might work together with the pyrroloquinoline quinone (PQQ) prosthetic group and the Ca(2+) ion in the catalytic turnover during methanol (CH(3)OH) oxidation. We purify MDH from Methylococcus capsulatus (Bath) with the disulfide bridge broken into two thiols. Spectroscopic and high-resolution X-ray crystallographic studies of this form of MDH indicate that the disulfide bridge is redox active. We observe an internal redox process within the holo-MDH that produces a disulfide radical anion concomitant with a companion PQQ radical, as evidenced by an optical absorption at 408 nm and a magnetically dipolar-coupled biradical in the EPR spectrum. These observations are corroborated by electron-density changes between the two cysteine sulfurs of the disulfide bridge as well as between the bound Ca(2+) ion and the O5-C5 bond of the PQQ in the high-resolution X-ray structure. On the basis of these findings, we propose a mechanism for the controlled redistribution of the two electrons during hydride transfer from the CH(3)OH in the alcohol oxidation without formation of the reduced PQQ ethenediol, a biradical mechanism that allows for possible recovery of the hydride for transfer to an external NAD(+) oxidant in the regeneration of the PQQ cofactor for multiple catalytic turnovers. In support of this mechanism, a steady-state level of the disulfide radical anion is observed during turnover of the MDH in the presence of CH(3)OH and NAD(+). | |||
Mechanism of Pyrroloquinoline Quinone-Dependent Hydride Transfer Chemistry from Spectroscopic and High-Resolution X-ray Structural Studies of the Methanol Dehydrogenase from Methylococcus capsulatus (Bath).,Chan SI, Chuankhayan P, Reddy Nareddy PK, Tsai IK, Tsai YF, Chen KH, Yu SS, Chen CJ J Am Chem Soc. 2021 Mar 10;143(9):3359-3372. doi: 10.1021/jacs.0c11414. Epub 2021 , Feb 25. PMID:33629832<ref>PMID:33629832</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7cdl" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Methanol dehydrogenase|Methanol dehydrogenase]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Methylococcus capsulatus str. Bath]] | ||
[[Category: Chan SI]] | |||
[[Category: Chen CJ]] | |||
[[Category: Chen KH-C]] | |||
[[Category: Chuankhayan P]] | |||
[[Category: Nareddy PKR]] | |||
[[Category: Tsai IK]] | |||
[[Category: Tsai YF]] | |||
[[Category: Yu SS-F]] | |||
Latest revision as of 19:06, 29 November 2023
holo-methanol dehydrogenase (MDH) with Cys131-Cys132 reduced from Methylococcus capsulatus (Bath)holo-methanol dehydrogenase (MDH) with Cys131-Cys132 reduced from Methylococcus capsulatus (Bath)
Structural highlights
FunctionPublication Abstract from PubMedThe active site of methanol dehydrogenase (MDH) contains a rare disulfide bridge between adjacent cysteine residues. As a vicinal disulfide, the structure is highly strained, suggesting it might work together with the pyrroloquinoline quinone (PQQ) prosthetic group and the Ca(2+) ion in the catalytic turnover during methanol (CH(3)OH) oxidation. We purify MDH from Methylococcus capsulatus (Bath) with the disulfide bridge broken into two thiols. Spectroscopic and high-resolution X-ray crystallographic studies of this form of MDH indicate that the disulfide bridge is redox active. We observe an internal redox process within the holo-MDH that produces a disulfide radical anion concomitant with a companion PQQ radical, as evidenced by an optical absorption at 408 nm and a magnetically dipolar-coupled biradical in the EPR spectrum. These observations are corroborated by electron-density changes between the two cysteine sulfurs of the disulfide bridge as well as between the bound Ca(2+) ion and the O5-C5 bond of the PQQ in the high-resolution X-ray structure. On the basis of these findings, we propose a mechanism for the controlled redistribution of the two electrons during hydride transfer from the CH(3)OH in the alcohol oxidation without formation of the reduced PQQ ethenediol, a biradical mechanism that allows for possible recovery of the hydride for transfer to an external NAD(+) oxidant in the regeneration of the PQQ cofactor for multiple catalytic turnovers. In support of this mechanism, a steady-state level of the disulfide radical anion is observed during turnover of the MDH in the presence of CH(3)OH and NAD(+). Mechanism of Pyrroloquinoline Quinone-Dependent Hydride Transfer Chemistry from Spectroscopic and High-Resolution X-ray Structural Studies of the Methanol Dehydrogenase from Methylococcus capsulatus (Bath).,Chan SI, Chuankhayan P, Reddy Nareddy PK, Tsai IK, Tsai YF, Chen KH, Yu SS, Chen CJ J Am Chem Soc. 2021 Mar 10;143(9):3359-3372. doi: 10.1021/jacs.0c11414. Epub 2021 , Feb 25. PMID:33629832[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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