Autocatalytic mechanism and consequences of covalent heme attachment in the cytochrome P4504A family
Autocatalytic mechanism and consequences of covalent heme attachment in the cytochrome P4504A family
复制标题
DOI：
10.1074/jbc.m112155200
复制
发表时间：
2002-04-12
影响因子：
4.8
通讯作者：
de Montellano, PRO
中科院分区：
文献类型：
--
作者：
LeBrun, LA;Hoch, U;de Montellano, PRO
细胞色素P450酶的CYP 4A家族中的辅血红素基团共价连接至I-螺旋谷氨酸残基。这种谷氨酸在CYP 4家族中是保守的，但在其他P450家族中不存在。如图所示，谷氨酸可能通过酯键与血红素5-甲基上的羟基连接。CYP 4A 1、CYP 4A 3和CYP 4A 11中谷氨酸突变为丙氨酸可抑制血红素共价结合。在野生型CYP 4A 3中，68%的血红素与异源表达的蛋白质共价结合，但在CYP 4A 3/E318 D突变体中，47%的血红素未发生变化，47%以非共价结合的5-羟甲基血红素存在，只有6%与蛋白质共价结合。在CYP 4A 3/E318 Q突变体中，大部分血红素未改变，
The prosthetic heme group in the CYP4A family of cytochrome P450 enzymes is covalently attached to an I-helix glutamic acid residue. This glutamic acid is conserved in the CYP4 family but is absent in other P450 families. As shown here, the glutamic acid is linked, presumably via an ester bond, to a hydroxyl group on the heme 5-methyl group. Mutation of the glutamic acid to an alanine in CYP4A1, CYP4A3, and CYP4A11 suppresses covalent heme binding. In wild-type CYP4A3 68% of the heme is covalently bound to the heterologously expressed protein, but in the CYP4A3/E318D mutant, 47% of the heme is unchanged, 47% is present as noncovalently bound 5-hydroxymethylheme, and only 6% is covalently bound to the protein. In the CYP4A3/ E318Q mutant, the majority of the heme is unaltered, and