Structural and biochemical characterization of MdaB from cariogenic Streptococcus mutans reveals an NADPH-specific quinone oxidoreductase

	Structural and biochemical characterization of MdaB from cariogenic Streptococcus mutans reveals an NADPH-specific quinone oxidoreductase
	Wang, ZX; Li, LF; 董宇辉;Dong, YH; Su, XD
刊名	ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
	2014
卷号	70 期号:4 页码:912-921
英文摘要	The smu. 1420 gene from the cariogenic pathogen Streptococcus mutans encodes a putative protein which has sequence homology to NQO [NAD(P) H: quinone oxidoreductase] family members, including mammalian NQO and bacterial MdaB (modulator of drug activity B). NQO can detoxify quinones by converting them to hydroquinones and prevent the generation of reactive oxygen species. Thus, comprehensive studies on Smu. 1420 will be important for uncovering the antioxidation and antidrug mechanisms of S. mutans. Here, the catalytic properties of Smu. 1420 have been characterized, and its structure was determined in complexes with NADP(+) and menadione, respectively. Smu. 1420 binds menadione directly and exhibits a pronounced preference for NADPH over NADH as a substrate, demonstrating that it is an NADPH-specific quinone oxidoreductase. The structure of Smu. 1420 shows a compact homodimer with two substrate pockets located in the cleft of the dimer interface. The nicotinamide moiety of NADP(+) is bound on top of the isoalloxazine moiety of the FAD cofactor and overlaps with the binding site of menadione, suggesting a hydride-transfer process from NADPH to FAD and then to menadione. Two strongly basic patches near the substrate pocket are expected to confer the preference for NADPH over NADH. These studies shed light on future drug development against the cariogenic pathogen S. mutans.
学科主题	Biochemistry & Molecular Biology; Biophysics; Crystallography
收录类别	SCI
WOS记录号	WOS:000333756700001
公开日期	2016-05-03
内容类型	期刊论文
源URL	[http://ir.ihep.ac.cn/handle/311005/224790]
专题	高能物理研究所_多学科研究中心
推荐引用方式 GB/T 7714	Wang, ZX,Li, LF,董宇辉；Dong, YH,et al. Structural and biochemical characterization of MdaB from cariogenic Streptococcus mutans reveals an NADPH-specific quinone oxidoreductase[J]. ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY,2014,70(4):912-921.
APA	Wang, ZX,Li, LF,董宇辉；Dong, YH,&Su, XD.(2014).Structural and biochemical characterization of MdaB from cariogenic Streptococcus mutans reveals an NADPH-specific quinone oxidoreductase.ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY,70(4),912-921.
MLA	Wang, ZX,et al."Structural and biochemical characterization of MdaB from cariogenic Streptococcus mutans reveals an NADPH-specific quinone oxidoreductase".ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY 70.4(2014):912-921.