Substrate-mediated electron transfer in peptidylglycine α-hydroxylating monooxygenase

Substrate-mediated electron transfer in peptidylglycine α-hydroxylating monooxygenase
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肽基甘氨酸 α-羟基化单加氧酶中底物介导的电子转移

DOI:
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发表时间:
1999
期刊:
Nature Structural Biology
影响因子:
--
通讯作者:
R. Mains
R. Mains
中科院分区:
--
文献类型:
--
作者:
L. Amzel;S. Prigge;A. Kolhekar;B. Eipper;R. Mains

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肽酰胺化是生物活性肽的一种普遍存在的翻译后修饰。肽基甘氨酸α-羟基化单加氧酶(PHM; EC 1.14.17.3)是催化该反应的第一步的酶,由两个结构域组成,每个结构域结合一个铜原子。铜在充满溶剂的畴间裂缝的两侧相距11 μ m,PHM反应需要在这些位点之间进行电子转移。一个合理的机制,电子转移可能涉及域间运动,以减少铜原子之间的距离。我们的实验表明,PHM催化核心(PHMcc)是酶活性的结晶相,其中域间运动是不可能的。相反,与催化相关的两种状态的结构表明,水,底物和活性位点残基可能提供了一个电子转移途径,只存在于PHM催化循环。
Peptide amidation is a ubiquitous posttranslational modification of bioactive peptides. Peptidylglycine α-hydroxylating monooxygenase (PHM; EC 1.14.17.3), the enzymne that catalyzes the first step of this reaction, is composed of two domains, each of which binds one copper atom. The coppers are held 11 Å apart on either side of a solvent-filled interdomain cleft, and the PHM reaction requires electron transfer between these sites. A plausible mechanism for electron transfer might involve interdomain motion to decrease the distance between the copper atoms. Our experiments show that PHM catalytic core (PHMcc) is enzymatically active in the crystal phase, where interdomain motion is not possible. Instead, structures of two states relevant to catalysis indicate that water, substrate and active site residues may provide an electron transfer pathway that exists only during the PHM catalytic cycle.
DOI: --
发表时间: 1984
期刊: The Journal of biological chemistry
影响因子: --
作者:
Westbrook,EM;Sigler,PB
通讯作者: Sigler,PB
DOI: 10.1073/pnas.95.16.9220
发表时间: 1998-08-04
影响因子: 11.1
作者:
Vásquez-Vivar, J;Kalyanaraman, B;Pritchard, KA
通讯作者: Pritchard, KA
双功能肽基甘氨酸α-酰胺化酶需要两个铜原子才能获得最大活性。
DOI: 10.1006/abbi.1994.1225
发表时间: 1994
影响因子: 3.9
作者:
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牛神经中间垂体肽基甘氨酸α-酰胺化单加氧酶的进一步表征。
DOI: 10.1210/mend-1-4-290
发表时间: 1987
期刊: Molecular endocrinology (Baltimore, Md.)
影响因子: --
作者:
Murthy,AS;Keutmann,HT;Eipper,BA
通讯作者: Eipper,BA