6es9: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Methylsuccinyl-CoA dehydrogenase of Paracoccus denitrificans with bound flavin adenine dinucleotide== | |||
<StructureSection load='6es9' size='340' side='right' caption='[[6es9]], [[Resolution|resolution]] 1.37Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6es9]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ES9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ES9 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6es9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6es9 OCA], [http://pdbe.org/6es9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6es9 RCSB], [http://www.ebi.ac.uk/pdbsum/6es9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6es9 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
(2S)-methylsuccinyl-CoA dehydrogenase (MCD) belongs to the family of FAD-dependent acyl-CoA dehydrogenase (ACD) and is a key enzyme of the ethylmalonyl-CoA pathway for acetate assimilation. It catalyzes the oxidation of (2S)-methylsuccinyl-CoA to alpha,beta-unsaturated mesaconyl-CoA and shows only about 0.5% activity with succinyl-CoA. Here we report the crystal structure of MCD at a resolution of 1.37 A. The enzyme forms a homodimer of two 60 kDa subunits. Compared to other ACDs, MCD contains a ~170 residue long N-terminal extension that structurally mimics a dimer-dimer interface of these enzymes that are canonically organized as tetramers. MCD catalyzes the unprecedented oxidation of an alpha-methyl branched dicarboxylic acid CoA thioester. Substrate specificity is achieved by a cluster of three arginines that accommodates the terminal carboxyl group and a dedicated cavity that facilitates binding of the C2 methyl branch. MCD apparently evolved towards preventing the unspecific oxidation of succinyl-CoA, a close structural homolog of (2S)-methylsuccinyl-CoA, and an essential intermediate in central carbon metabolism. For different metabolic engineering and biotechnological applications, however, an enzyme that can oxidize succinyl-CoA to fumaryl-CoA is sought after. Based on the MCD structure, we were able to shift substrate specificity of MCD towards succinyl-CoA through active site mutagenesis. | |||
Structural basis for substrate specificity of methylsuccinyl-CoA dehydrogenase: an unusual member of the acyl-CoA dehydrogenase family.,Schwander T, McLean R, Zarzycki J, Erb TJ J Biol Chem. 2017 Dec 22. pii: RA117.000764. doi: 10.1074/jbc.RA117.000764. PMID:29275330<ref>PMID:29275330</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6es9" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Erb, T J]] | |||
[[Category: Schwander, T]] | [[Category: Schwander, T]] | ||
[[Category: | [[Category: Zarzycki, j]] | ||
[[Category: | [[Category: Acyl-coa dehydrogenase]] | ||
[[Category: Ethylmalonyl-coa pathway]] | |||
[[Category: Flavin adenine dinucleotide]] | |||
[[Category: Flavoprotein]] | |||
[[Category: Methylsuccinyl-coa]] | |||
