View source for 5ujc


==Crystal structure of a C.elegans B12-trafficking protein CblC, a human MMACHC homologue==
<StructureSection load='5ujc' size='340' side='right'caption='[[5ujc]], [[Resolution|resolution]] 1.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ujc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Caenorhabditis_elegans Caenorhabditis elegans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UJC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UJC 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]] 1.35&#8491;</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=TAR:D(-)-TARTARIC+ACID'>TAR</scene>, <scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</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=5ujc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ujc OCA], [https://pdbe.org/5ujc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ujc RCSB], [https://www.ebi.ac.uk/pdbsum/5ujc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ujc ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MMAC_CAEEL MMAC_CAEEL] Catalyzes the reductive dealkylation of cyanocobalamin to cob(II)alamin, using FAD or FMN as cofactor and NADPH as cosubstrate. Can also catalyze the glutathione-dependent reductive demethylation of methylcobalamin, and, with much lower efficiency, the glutathione-dependent reductive demethylation of adenosylcobalamin. Under anaerobic conditions cob(I)alamin is the first product; it is highly reactive and is converted to aquocob(II)alamin in the presence of oxygen. Binds cyanocobalamin, adenosylcobalamin, methylcobalamin and other, related vitamin B12 derivatives.[UniProtKB:Q9Y4U1]
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== Publication Abstract from PubMed ==
The cobalamin or B12 cofactor supports sulfur and one-carbon metabolism and the catabolism of odd-chain fatty acids, branched-chain amino acids and cholesterol. CblC is a B12 processing enzyme involved in an early cytoplasmic step in the cofactor trafficking pathway. It catalyzes the glutathione (GSH)-dependent dealkylation of alkylcobalamins and the reductive decyanation of cyanocobalamin. CblC from Caenorhabdiitis elegans (ceCblC) also exhibits a robust thiol oxidase activity converting reduced GSH to oxidized GSSG with concomitant scrubbing of ambient dissolved O2 The mechanism of thiol oxidation catalyzed by ceCblC is not known. In this study, we demonstrate that novel coordination chemistry accessible to ceCblC-bound cobalamin, supports its thiol oxidase activity via a glutathionyl-cobalamin intermediate. Deglutathionylation of glutathionyl-cobalamin by a second molecule of GSH yields GSSG. The crystal structure of ceCblC provides insights into how architectural differences at the alpha- and beta-faces of cobalamin promote the thiol oxidase activity of ceCblC but mute it in wild-type human CblC. The R161G and R161Q mutations in human CblC unmask its latent thiol oxidase activity and are correlated with increased cellular oxidative stress disease. In summary, we have uncovered key architectural features in the cobalamin-binding pocket that support unusual cob(II)alamin coordination chemistry and enable the thiol oxidase activity of ceCblC.

Coordination Chemistry Controls the Thiol Oxidase Activity of the B12 Trafficking Protein CblC.,Li Z, Shanmuganathan A, Ruetz M, Yamada K, Lesniak NA, Kraeutler B, Brunold TC, Koutmos M, Banerjee R J Biol Chem. 2017 Apr 25. pii: jbc.M117.788554. doi: 10.1074/jbc.M117.788554. PMID:28442570<ref>PMID:28442570</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5ujc" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Caenorhabditis elegans]]
[[Category: Large Structures]]
[[Category: Banerjee R]]
[[Category: Brunold TC]]
[[Category: Koutmos M]]
[[Category: Krautler B]]
[[Category: Lesniak NA]]
[[Category: Li Z]]
[[Category: Ruetz M]]
[[Category: Shanmuganathan A]]
[[Category: Yamada K]]