Crystal structure of carbapenem synthase (CarC)
Crystal structure of carbapenem synthase (CarC)
复制标题
DOI：
10.1074/jbc.m213054200
复制
发表时间：
2003-06-06
影响因子：
4.8
通讯作者：
Schofield, CJ
中科院分区：
文献类型：
--
作者：
Clifton, IJ;Doan, LX;Schofield, CJ
碳青霉烯类抗生素的生物合成途径是在铁和2-氧戊二酸依赖的加氧酶（CarC）催化下，通过碳青霉烯胺的外映体化/去饱和进行的。CarC与Fe（II）和2-氧葡萄糖酸盐络合的晶体结构显示其为六聚体（空间群C2221），与溶液研究一致。CarC单体含有双链β -螺旋核心，支持配体结合单个Fe(II)， 2-氧葡萄糖酸酯以双齿方式配合。得到了l - n -乙酰脯氨酸作为底物类似物的结构。利用碳青霉烯类和碳青霉烯类立体异构体的量子力学/分子力学模型研究底物结合。这项联合工作将促进进一步的机制研究，并有助于碳青霉烯类生物合成的工程。
The proposed biosynthetic pathway to the carbapenem antibiotics proceeds via epimerization/desaturation of a carbapenam in an unusual process catalyzed by an iron- and 2-oxoglutarate-dependent oxygenase, CarC. Crystal structures of CarC complexed with Fe(II) and 2-oxoglutarate reveal it to be hexameric (space group C2221), consistent with solution studies. CarC monomers contain a double-stranded beta-helix core that supports ligands binding a single Fe(II) to which 2-oxoglutarate complexes in a bi-dentate manner. A structure was obtained with L-N-acetylproline acting as a substrate analogue. Quantum mechanical/molecular mechanical modeling studies with stereoisomers of carbapenams and carbapenems were used to investigate substrate binding. The combined work will stimulate further mechanistic studies and aid in the engineering of carbapenem biosynthesis.