Re-evaluation of amino acid sequence and structural consensus rules for cysteine-nitric oxide reactivity
Re-evaluation of amino acid sequence and structural consensus rules for cysteine-nitric oxide reactivity
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DOI：
10.1515/bc.2000.081
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发表时间：
2000-07-01
影响因子：
3.7
通讯作者：
Bolognesi, M
中科院分区：
文献类型：
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作者：
Ascenzi, P;Colasanti, M;Bolognesi, M
一氧化氮合酶(NO)是由不同细胞类型的L精氨酸在一氧化氮合酶的作用下转化为L的瓜氨酸而产生的，它在多种生理和病理事件中发挥作用。亚硝硫醇的形成和分解的巨大倾向表明了一种机制，即调节在其活性中心和/或变构位置含有非反应性半胱氨酸残基的大分子的作用。根据人血红蛋白(Hb)的结构，考虑到已知的酸碱催化的Cysβ93-亚硝化和Cysβ93-NO-脱氮过程，推测的氨基酸序列(Lys/Arg/His/Asp/Glu)Cys(Asp/Glu)(分别为-1、0和+1位)被认为是Cys-NO反应的最低共识基序。虽然在人类Hb中没有发现，但在一些无反应蛋白序列(如NMDA受体)中，已观察到在-2位置存在极性氨基酸残基(Gly/Ser/Thr/Cys/Tyr/Asn/Gln)。然而，三肽或四肽共识基序中最重要的成分被认为是半胱氨酸(Asp/Glu)对[Stamler et at，Neuron(1997)18,691-696]。在这里，我们分析了几种含有非反应性半胱氨酸残基的蛋白质的三维结构，并表明它们的亚硝化和反硝化过程可能取决于半胱氨酸-半胱氨酸的原子结构微环境，而不是三或四肽序列的共识基序。
Nitric oxide (NO), produced in different cell types through the conversion of L-arginine into L-citrulline by the enzyme NO synthase, has been proposed to exert its action in several physiological and pathological events. The great propensity for nitrosothiol formation and breakdown represents a mechanism which modulates the action of macromolecules containing NO-reactive Cys residues at their active centre and/or allosteric sites. Based on the human haemoglobin (Hb) structure and accounting for the known acid-base catalysed Cys beta 93-nitrosylation and Cys beta 93NO-denitrosylation processes, the putative amino acid sequence (Lys/Arg/His/Asp/Glu)Cys(Asp/Glu) (sites -1, 0, and + 1, respectively) has been proposed as the minimum consensus motif for Cys-NO reactivity. Although not found in human Hb, the presence of a polar amino acid residue (Gly/Ser/Thr/Cys/Tyr/Asn/Gln) at the -2 position has been observed in some NO-reactive protein sequences (e.g., NMDA receptors). However, the most important component of the tri- or tetra-peptide consensus motif has been recognised as the Cys(Asp/Glu) pair [Stamler et at, Neuron (1997) 18, 691-696]. Here, we analyse the three-dimensional structure of several proteins containing NO-reactive Cys residues, and show that their nitrosylation and denitrosylation processes may depend on the Cys-Sy atomic structural microenvironment rather than on the tri- or tetra-peptide sequence consensus motif.