6et9 | pdb_00006et9

Structure of the acetoacetyl-CoA-thiolase/HMG-CoA-synthase complex from Methanothermococcus thermolithotrophicus at 2.75 A

spinqualitylabelsall models 6et9, resolution 2.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6et9 is a 12 chain structure with sequence from Methanothermococcus thermolithotrophicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.75Å Ligands: CL, GOL, K, MG, NA, TRS, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A384E138_METTL Publication Abstract from PubMed Many reactions within a cell are thermodynamically unfavorable. To efficiently run some of those endergonic reactions, nature evolved intermediate-channeling enzyme complexes, in which the products of the first endergonic reactions are immediately consumed by the second exergonic reactions. Based on this concept, we studied how archaea overcome the unfavorable first reaction of isoprenoid biosynthesis-the condensation of two molecules of acetyl-CoA to acetoacetyl-CoA catalyzed by acetoacetyl-CoA thiolases (thiolases). We natively isolated an enzyme complex comprising the thiolase and 3-hydroxy-3-methylglutaryl (HMG)-CoA synthase (HMGCS) from a fast-growing methanogenic archaeon, Methanothermococcus thermolithotrophicus HMGCS catalyzes the second reaction in the mevalonate pathway-the exergonic condensation of acetoacetyl-CoA and acetyl-CoA to HMG-CoA. The 380-kDa crystal structure revealed that both enzymes are held together by a third protein (DUF35) with so-far-unknown function. The active-site clefts of thiolase and HMGCS form a fused CoA-binding site, which allows for efficient coupling of the endergonic thiolase reaction with the exergonic HMGCS reaction. The tripartite complex is found in almost all archaeal genomes and in some bacterial ones. In addition, the DUF35 proteins are also important for polyhydroxyalkanoate (PHA) biosynthesis, most probably by functioning as a scaffold protein that connects thiolase with 3-ketoacyl-CoA reductase. This natural and highly conserved enzyme complex offers great potential to improve isoprenoid and PHA biosynthesis in biotechnologically relevant organisms. Archaeal acetoacetyl-CoA thiolase/HMG-CoA synthase complex channels the intermediate via a fused CoA-binding site.,Vogeli B, Engilberge S, Girard E, Riobe F, Maury O, Erb TJ, Shima S, Wagner T Proc Natl Acad Sci U S A. 2018 Mar 12. pii: 1718649115. doi:, 10.1073/pnas.1718649115. PMID:29531083 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Thiolase 3D structures

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