The crystal structure of human S-adenosylmethionine decarboxylase at 2.25 Å resolution reveals a novel fold
The crystal structure of human S-adenosylmethionine decarboxylase at 2.25 Å resolution reveals a novel fold
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DOI：
10.1016/s0969-2126(99)80074-4
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发表时间：
1999-05-01
期刊：
影响因子：
5.7
通讯作者：
Ealick, SE
中科院分区：
文献类型：
--
作者：
Ekstrom, JL;Mathews, II;Ealick, SE
背景资料：S-腺苷甲硫氨酸脱羧酶（S-Adenosylmethionine decarboxylase，S-MetDC）是多胺合成途径中的关键调节酶，也是一个研究较多的药物靶点。所述CDMetDC脱羧反应依赖于通过分子内酶原自切割反应产生的乙酰基辅因子。腐胺可增强前酶处理和底物脱羧反应的变构性。这种酶的结构解析对于充分解释现有的突变和底物结合数据是必要的，并建议进一步的实验研究，结果：基于22个硒原子位置，使用多波长反常衍射（MAD）定相方法，已经确定了人BmMetDC的结构，分辨率为2.25 A。（α β）（2）二聚体，其中α和β表示酶原自切割反应的产物。每个（α-β）单体的架构是一种新的四层α/β-夹心fold，由两个反平行的八链β片两侧的几个α和3（10）helices.Conclusions：的结构和拓扑结构的METDC显示内部对称性，这表明这种蛋白质可能是一个古老的基因复制的产物。保守的，功能上重要的残基的位置表明活性位点的位置和效应分子腐胺的一个可能的结合位点。
Background: S-Adenosylmethionine decarboxylase (AdoMetDC) is a critical regulatory enzyme of the polyamine synthetic pathway, and a well-studied drug target. The AdoMetDC decarboxylation reaction depends upon a pyruvoyl cofactor generated via an intramolecular proenzyme self-cleavage reaction. Both the proenzyme-processing and substrate-decarboxylation reactions are allosterically enhanced by putrescine. Structural elucidation of this enzyme is necessary to fully interpret the existing mutational and inhibitor-binding data, and to suggest further experimental studies,Results: The structure of human AdoMetDC has been determined to 2.25 A resolution using multiwavelength anomalous diffraction (MAD) phasing methods based on 22 selenium-atom positions, The quaternary structure of the mature AdoMetDC is an (alpha beta)(2) dimer, where alpha and beta represent the products of the proenzyme self-cleavage reaction. The architecture of each (alpha beta) monomer is a novel four-layer alpha/beta-sandwich fold, comprised of two antiparallel eight-stranded beta sheets flanked by several alpha and 3(10) helices.Conclusions: The structure and topology of AdoMetDC display internal symmetry, suggesting that this protein may be the product of an ancient gene duplication. The positions of conserved, functionally important residues suggest the location of the active site and a possible binding site for the effector molecule putrescine.