A conserved mechanism for sulfonucleotide reduction.
A conserved mechanism for sulfonucleotide reduction.
复制标题
DOI：
10.1371/journal.pbio.0030250
复制
发表时间：
2005-08
期刊：
影响因子：
9.8
通讯作者：
Bertozzi CR
中科院分区：
文献类型：
--
作者：
Carroll KS;Gao H;Chen H;Stout CD;Leary JA;Bertozzi CR
磺核苷酸还原酶是一个多样化的酶家族，催化还原硫同化的第一步。在这个反应中，活化的硫酸盐在腺苷-5 ' -磷酸硫酸酯（APS）或3 ' -磷酸腺苷-5 ' -磷酸硫酸酯（PAPS）的环境下与硫氧还蛋白的还原等效物一起转化为亚硫酸盐。在该反应中产生的亚硫酸盐在细菌和植物中被用于最终产生必需的生物分子，如半胱氨酸和辅酶a。人类不具有同源代谢途径，因此，这些酶是治疗干预的有吸引力的靶点。本研究采用质谱和生化相结合的方法，研究了人结核分枝杆菌APS还原酶还原磺胺基核苷酸的机制。该结果支持了两步机制的假设，其中磺核苷酸首先经历快速亲核攻击，形成酶-硫代磺酸盐（E-Cys-S-SO3−）中间体。亚硫酸盐随后以依赖硫氧还原素的方式释放。来自结构不同亚类的其他磺核苷酸还原酶似乎使用相同的机制，这表明该酶家族是从一个共同的祖先进化而来的。催化硫同化第一步的多种酶家族具有相同的机制。
Sulfonucleotide reductases are a diverse family of enzymes that catalyze the first committed step of reductive sulfur assimilation. In this reaction, activated sulfate in the context of adenosine-5′-phosphosulfate (APS) or 3′-phosphoadenosine 5′-phosphosulfate (PAPS) is converted to sulfite with reducing equivalents from thioredoxin. The sulfite generated in this reaction is utilized in bacteria and plants for the eventual production of essential biomolecules such as cysteine and coenzyme A. Humans do not possess a homologous metabolic pathway, and thus, these enzymes represent attractive targets for therapeutic intervention. Here we studied the mechanism of sulfonucleotide reduction by APS reductase from the human pathogen Mycobacterium tuberculosis, using a combination of mass spectrometry and biochemical approaches. The results support the hypothesis of a two-step mechanism in which the sulfonucleotide first undergoes rapid nucleophilic attack to form an enzyme-thiosulfonate (E-Cys-S-SO3 −) intermediate. Sulfite is then released in a thioredoxin-dependent manner. Other sulfonucleotide reductases from structurally divergent subclasses appear to use the same mechanism, suggesting that this family of enzymes has evolved from a common ancestor. A diverse family of enzymes that catalyze the first step in sulfur assimilation share the same mechanism.
登录
查看更多内容
DOI：
10.1016/j.ijbiomac.2003.08.010
发表时间：
2003-12-01
影响因子：
8.2
作者：
Cicero, DO;Melino, S;Paci, M
通讯作者：
Paci, M
影响因子：
7.4
作者：
Hernández, H;Hewitson, KS;Robinson, CV
通讯作者：
Robinson, CV
影响因子：
7.4
作者：
Johnson, KA;Verhagen, MFJM;Amster, IJ
通讯作者：
Amster, IJ
DOI：
10.1073/pnas.94.12.6087
发表时间：
1997-06-10
影响因子：
11.1
作者：
Khoroshilova, N;Popescu, C;Kiley, PJ
通讯作者：
Kiley, PJ
DOI：
10.1111/j.1432-1033.1995.347_1.x
发表时间：
1995-10-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
BERENDT, U;HAVERKAMP, T;SCHWENN, JD
通讯作者：
SCHWENN, JD