Journal article
Furfural reduction mechanism of a zinc-dependent alcohol dehydrogenase from Cupriavidus necator JMP134
Molecular microbiology, Vol.83(1), pp.85-95
01/2012
Handle:
https://hdl.handle.net/2376/115121
PMCID: PMC3551575
PMID: 22081946
Abstract
FurX is a tetrameric Zn-dependent alcohol dehydrogenase (ADH) from
Cupriavidus necator
JMP134. The enzyme rapidly reduces furfural with NADH as the reducing power. For the first time among characterized ADHs, the high-resolution structures of all reaction steps were obtained in a time-resolved manner, thereby illustrating the complete catalytic events of NADH-dependent reduction of furfural and the dynamic Zn
2+
coordination among Glu66, water, substrate and product. In the fully closed conformation of the NADH complex, the catalytic turnover proved faster than observed for the partially closed conformation due to an effective proton transfer network. The domain motion triggered by NAD(H) association/dissociation appeared to facilitate dynamic interchanges in Zn
2+
coordination with substrate and product molecules, ultimately increasing the enzymatic turnover rate. NAD
+
dissociation appeared to be a slow process, involving multiple steps in concert with a domain opening and reconfiguration of Glu66. This agrees with the report that the cofactor is not dissociated from FurX during ethanol-dependent reduction of furfural, in which ethanol reduces NAD
+
to NADH that is subsequently used for furfural reduction.
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Details
- Title
- Furfural reduction mechanism of a zinc-dependent alcohol dehydrogenase from Cupriavidus necator JMP134
- Creators
- ChulHee Kang - School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USARobert Hayes - Department of Chemistry, Washington State University, Pullman, WA 99164, USAEmiliano J Sanchez - School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USABrian N Webb - Department of Chemistry, Washington State University, Pullman, WA 99164, USAQunrui Li - School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USATravis Hooper - Department of Chemistry, Washington State University, Pullman, WA 99164, USAMark S Nissen - Department of Chemistry, Washington State University, Pullman, WA 99164, USALuying Xun - School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USA
- Publication Details
- Molecular microbiology, Vol.83(1), pp.85-95
- Academic Unit
- Chemistry, Department of; Molecular Biosciences, School of
- Grant note
- T32 GM008336 || GM / National Institute of General Medical Sciences : NIGMS
- Identifiers
- 99900548343701842
- Language
- English
- Resource Type
- Journal article