Structure and mechanism of mouse cysteine dioxygenase

被引：164

作者：

McCoy, JG

Bailey, LJ

Bitto, E

Bingman, CA

Aceti, DJ

Fox, BG

Phillips, GN

机构：

[1] Univ Wisconsin, Ctr Eukaryot Struct Gen, Madison, WI 53705 USA

[2] Univ Wisconsin, Dept Biochem, Madison, WI 53705 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2006年 / 103卷 / 09期

关键词：

cupin; cysteine metabolism; O-2-activation;

D O I：

10.1073/pnas.0509262103

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Cysteine dioxygenase (CDO) catalyzes the oxidation of L-cysteine to cysteine sulfinic acid. Deficiencies in this enzyme have been linked to autoimmune diseases and neurological disorders. The x-ray crystal structure of CDO from Mus musculus was solved to a nominal resolution of 1.75 angstrom. The sequence is 91% identical to that of a human homolog. The structure reveals that CDO adopts the typical beta-barrel fold of the cupin superfamily. The NE2 atoms of His-86, -88, and -140 provide the metal binding site. The structure further revealed a covalent linkage between the side chains of Cys-93 and Tyr-157, the cysteine of which is conserved only in eukaryotic proteins. Metal analysis showed that the recombinant enzyme contained a mixture of iron, nickel, and zinc, with increased iron content associated with increased catalytic activity. Details of the predicted active site are used to present and discuss a plausible mechanism of action for the enzyme.

引用

页码：3084 / 3089

页数：6

共 47 条

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