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==Structure of Human ATP:Cobalamin Adenosyltransferase R190C bound to adenosylcobalamin==
<StructureSection load='7ruu' size='340' side='right'caption='[[7ruu]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RUU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RUU 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]] 1.85&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5AD:5-DEOXYADENOSINE'>5AD</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=B12:COBALAMIN'>B12</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</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=7ruu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ruu OCA], [https://pdbe.org/7ruu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ruu RCSB], [https://www.ebi.ac.uk/pdbsum/7ruu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ruu ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
Human ATP:cob(I)alamin adenosyltransferase (ATR) is a mitochondrial enzyme that catalyzes an adenosyl transfer to cob(I)alamin, synthesizing 5 -deoxyadenosylcobalamin (AdoCbl) or coenzyme B12. ATR is also a chaperone that escorts AdoCbl, transferring it to methylmalonyl-CoA mutase, which is important in propionate metabolism. Mutations in ATR lead to methylmalonic aciduria type B (or MMAB), an inborn error of B12metabolism. Our previous studies have furnished insights into how ATR protein dynamics influence redox-linked cobalt coordination chemistry, controlling its catalytic versus chaperone functions. In this study, we have characterized three patient mutations at two conserved active site residues in human ATR, R190C/H and E193K, and obtained crystal structures of R190C and E193K variants, which display only subtle structural changes. All three mutations were found to weaken affinities for the cob(II)alamin substrate and the AdoCbl product and increase KM(ATP). (31) P NMR studies show that binding of the triphosphate product, formed during the adenosylation reaction, is also weakened. However, while the kcatof this reaction is significantly diminished for the R190C/H mutants, it is comparable to wild-type enzyme for the E193K variant, revealing the catalytic importance of Arg-190. Furthermore, while the E193K mutation selectively impairs the chaperone function by promoting product release into solution, its catalytic function might be unaffected at physiological ATP concentrations. In contrast, the R190C/H mutations affect both the catalytic and chaperoning activities of ATR. Since the E193K mutation spares the catalytic activity of ATR, our data suggest that patients carrying this mutation are more likely to be responsive to cobalamin therapy.

Patient mutations in human ATP:cob(I)alamin adenosyltransferase differentially affect its catalytic versus chaperone functions.,Gouda H, Mascarenhas R, Pillay S, Ruetz M, Koutmos M, Banerjee R J Biol Chem. 2021 Oct 29:101373. doi: 10.1016/j.jbc.2021.101373. PMID:34757128<ref>PMID:34757128</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Banerjee R]]
[[Category: Gouda H]]
[[Category: Koutmos M]]
[[Category: Mascarenhas R]]