6t92
NAD+-dependent fungal formate dehydrogenase from Chaetomium thermophilum: A complex of N120C mutant protein with the reduced form of the cofactor NADH and the substrate formate at a secondary site.NAD+-dependent fungal formate dehydrogenase from Chaetomium thermophilum: A complex of N120C mutant protein with the reduced form of the cofactor NADH and the substrate formate at a secondary site.
Structural highlights
FunctionFDH_CHATD Catalyzes the NAD(+)-dependent oxidation of formate to carbon dioxide. Formate oxidation is the final step in the methanol oxidation pathway in methylotrophic microorganisms. Has a role in the detoxification of exogenous formate in non-methylotrophic organisms.[HAMAP-Rule:MF_03210][REFERENCE:2] Publication Abstract from PubMedThe removal of carbon dioxide from the waste streams of industrial processes is a major challenge for creation of a sustainable circular economy. This makes the synthesis of formate from CO2 by NAD(+) dependent formate dehydrogenases (FDHs) an attractive process for this purpose. The efficiency of this reaction is however low and to achieve a viable industrial process an optimised engineered enzyme needs to be developed. In order to understand the detailed enzymatic mechanism of catalysis structures of different cofactor and substrate complexes of the FDH from the thermophilic filamentous fungus, Chaetomium thermophilum have been determined to 1.2-1.3 A resolution. The substrate formate is shown to be held by four hydrogen bonds in the FDH catalytic site within the ternary complex with substrate and NAD(+)and a secondary formate binding site is observed in crystals soaked with substrate. Water molecules are excluded from the FDH catalytic site when the substrate is bound. The angle between the plane of the NAD(+) cofactor pyridine ring and the plane of the formate molecule is around 27 degrees . Additionally, structures of a FDH mutant enzyme, N120C, in complex with the reduced form of the cofactor have also been determined both in the presence and absence of formate bound at the secondary site. These structures provide further understanding of the catalytic mechanism of this fungal enzyme. Structural insights into the NAD(+)-dependent formate dehydrogenase mechanism revealed from the NADH complex and the formate NAD(+) ternary complex of the Chaetomium thermophilum enzyme.,Yilmazer B, Isupov MN, De Rose SA, Bulut H, Benninghoff JC, Binay B, Littlechild JA J Struct Biol. 2020 Dec 1;212(3):107657. doi: 10.1016/j.jsb.2020.107657. Epub, 2020 Oct 24. PMID:33148525[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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