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New page: left|200px<br /><applet load="1req" size="450" color="white" frame="true" align="right" spinBox="true" caption="1req, resolution 2.0Å" /> '''METHYLMALONYL-COA MUT...
 
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[[Image:1req.gif|left|200px]]<br /><applet load="1req" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1req, resolution 2.0&Aring;" />
'''METHYLMALONYL-COA MUTASE'''<br />


==Overview==
==METHYLMALONYL-COA MUTASE==
BACKGROUND. The enzyme methylmalonyl-coenzyme A (CoA) mutase, an alphabeta, heterodimer of 150 kDa, is a member of a class of enzymes that uses, coenzyme B12 (adenosylcobalamin) as a cofactor. The enzyme induces the, formation of an adenosyl radical from the cofactor. This radical then, initiates a free-radical rearrangement of its substrate, succinyl-CoA, to, methylmalonyl-CoA. RESULTS. Reported here is the crystal structure at 2 A, resolution of methylmalonyl-CoA mutase from Propionibacterium shermanii in, complex with coenzyme B12 and with the partial substrate desulpho-CoA, (lacking the succinyl group and the sulphur atom of the substrate). The, coenzyme is bound by a domain which shares a similar fold to those of, flavodoxin and the B12-binding domain of methylcobalamin-dependent, methionine synthase. The cobalt atom is coordinated, via a long bond, to a, histidine from the protein. The partial substrate is bound along the axis, of a (beta/alpha)8 TIM barrel domain. CONCLUSIONS. The histidine-cobalt, distance is very long (2.5 A compared with 1.95-2.2 A in free cobalamins), suggesting that the enzyme positions the histidine in order to weaken the, metal-carbon bond of the cofactor and favour the formation of the initial, radical species. The active site is deeply buried, and the only access to, it is through a narrow tunnel along the axis of the TIM barrel domain.
<StructureSection load='1req' size='340' side='right'caption='[[1req]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1req]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Propionibacterium_freudenreichii_subsp._shermanii Propionibacterium freudenreichii subsp. shermanii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1REQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1REQ 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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DCA:DESULFO-COENZYME+A'>DCA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=1req FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1req OCA], [https://pdbe.org/1req PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1req RCSB], [https://www.ebi.ac.uk/pdbsum/1req PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1req ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MUTB_PROFR MUTB_PROFR] Catalyzes the isomerization of succinyl-CoA to methylmalonyl-CoA during synthesis of propionate from tricarboxylic acid-cycle intermediates.
== 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/re/1req_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=1req ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
BACKGROUND. The enzyme methylmalonyl-coenzyme A (CoA) mutase, an alphabeta heterodimer of 150 kDa, is a member of a class of enzymes that uses coenzyme B12 (adenosylcobalamin) as a cofactor. The enzyme induces the formation of an adenosyl radical from the cofactor. This radical then initiates a free-radical rearrangement of its substrate, succinyl-CoA, to methylmalonyl-CoA. RESULTS. Reported here is the crystal structure at 2 A resolution of methylmalonyl-CoA mutase from Propionibacterium shermanii in complex with coenzyme B12 and with the partial substrate desulpho-CoA (lacking the succinyl group and the sulphur atom of the substrate). The coenzyme is bound by a domain which shares a similar fold to those of flavodoxin and the B12-binding domain of methylcobalamin-dependent methionine synthase. The cobalt atom is coordinated, via a long bond, to a histidine from the protein. The partial substrate is bound along the axis of a (beta/alpha)8 TIM barrel domain. CONCLUSIONS. The histidine-cobalt distance is very long (2.5 A compared with 1.95-2.2 A in free cobalamins), suggesting that the enzyme positions the histidine in order to weaken the metal-carbon bond of the cofactor and favour the formation of the initial radical species. The active site is deeply buried, and the only access to it is through a narrow tunnel along the axis of the TIM barrel domain.


==About this Structure==
How coenzyme B12 radicals are generated: the crystal structure of methylmalonyl-coenzyme A mutase at 2 A resolution.,Mancia F, Keep NH, Nakagawa A, Leadlay PF, McSweeney S, Rasmussen B, Bosecke P, Diat O, Evans PR Structure. 1996 Mar 15;4(3):339-50. PMID:8805541<ref>PMID:8805541</ref>
1REQ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Propionibacterium_freudenreichii_subsp._shermanii Propionibacterium freudenreichii subsp. shermanii] with B12, DCA and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Methylmalonyl-CoA_mutase Methylmalonyl-CoA mutase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.4.99.2 5.4.99.2] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1REQ OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
How coenzyme B12 radicals are generated: the crystal structure of methylmalonyl-coenzyme A mutase at 2 A resolution., Mancia F, Keep NH, Nakagawa A, Leadlay PF, McSweeney S, Rasmussen B, Bosecke P, Diat O, Evans PR, Structure. 1996 Mar 15;4(3):339-50. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=8805541 8805541]
</div>
[[Category: Methylmalonyl-CoA mutase]]
<div class="pdbe-citations 1req" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Propionibacterium freudenreichii subsp. shermanii]]
[[Category: Propionibacterium freudenreichii subsp. shermanii]]
[[Category: Protein complex]]
[[Category: Evans PR]]
[[Category: Evans, P.R.]]
[[Category: Mancia F]]
[[Category: Mancia, F.]]
[[Category: B12]]
[[Category: DCA]]
[[Category: GOL]]
[[Category: intramolecular transferase]]
[[Category: isomerase]]
[[Category: mutase]]
 
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