3o3o

(R)-2-hydroxyisocaproyl-CoA dehydratase in complex with (R)-2-hydroxyisocaproate

spinqualitylabelsall models 3o3o, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3o3o is a 2 chain structure with sequence from Clostridioides difficile. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: 2RH, H2S Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function HADB_CLODI Involved in the reductive branch of L-leucine fermentation. Catalyzes the irreversible beta/alpha-elimination of water from (R)-2-hydroxyisocaproyl-CoA to yield isocaprenoyl-CoA. This beta/alpha-dehydration depends on the reductive formation of ketyl radicals on the substrate generated by injection of a single electron from the ATP-dependent activator protein HadI. The enzyme is specific for the R-isomer. Publication Abstract from PubMed The radical enzyme (R)-2-hydroxyisocaproyl-CoA dehydratase catalyzes the dehydration of (R)-2-hydroxyisocaproyl-CoA in the fermentation of l-leucine by the human pathogenic bacterium Clostridium difficile. In contrast to other radical enzymes, such as bacterial class II ribonucleotide reductase or biotin synthase, the Fe/S cluster containing (R)-2-hydroxyisocaproyl-CoA dehydratase requires no special cofactors such as coenzyme B(12) or S-adenosylmethionine for radical generation. Instead it uses a single high-energy electron that is recycled after each turnover. The catalyzed reaction, an atypical alpha/beta-dehydration, depends on the reductive formation of ketyl radicals on the substrate generated by injection of a single electron from the ATP-dependent activator protein. So far, it is unknown how the active electron is recycled and how unwanted side reactions are prevented, allowing for up to 10 000 turnovers. The crystal structure reveals that the heterodimeric protein contains two [4Fe-4S] clusters at a distance of 12 A, each coordinated by three cysteines and one terminal ligand. The cluster in the alpha-subunit is part of the active site. In the absence of substrate, a water/hydroxide ion acts as the fourth ligand. The substrate replaces this ligand and coordinates the cluster via the carbonyl-oxygen of the thioester group. The cluster in the beta-subunit has a terminal sulfhydryl/sulfido ligand and can act as a reservoir to protect the electron from unwanted side reactions via a recycling mechanism. The crystal structure of (R)-2-hydroxyisocaproyl-CoA dehydratase serves as a model for the reductively radical-generating metalloenzymes of the (R)-2-hydroxyacyl-CoA dehydratase and benzoyl-CoA reductase families. Structural Basis for Reductive Radical Formation and Electron Recycling in (R)-2-Hydroxyisocaproyl-CoA Dehydratase.,Knauer SH, Buckel W, Dobbek H J Am Chem Soc. 2011 Mar 2. PMID:21366233 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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