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首页> 外文期刊>Journal of Molecular Biology >Modulation of an active-site cysteine pKa allows PDI to act as a catalyst of both disulfide bond formation and isomerization.
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Modulation of an active-site cysteine pKa allows PDI to act as a catalyst of both disulfide bond formation and isomerization.

机译：活性位点半胱氨酸pKa的调节允许PDI充当二硫键形成和异构化的催化剂。

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摘要

Protein disulfide isomerase (PDI) plays a central role in disulfide bond formation in the endoplasmic reticulum. It is implicated both in disulfide bond formation and in disulfide bond reduction and isomerization. To be an efficient catalyst of all three reactions requires complex mechanisms. These include mechanisms to modulate the pK(a) values of the active-site cysteines of PDI. Here, we examined the role of arginine 120 in modulating the pK(a) values of these cysteines. We find that arginine 120 plays a significant role in modulating the pK(a) of the C-terminal active-site cysteine in the a domain of PDI and plays a role in determining the reactivity of the N-terminal active-site cysteine but not via direct modulation of its pK(a). Mutation of arginine 120 and the corresponding residue, arginine 461, in the a' domain severely reduces the ability of PDI to catalyze disulfide bond formation and reduction but enhances the ability to catalyze disulfide bond isomerization due to the formation of more stable PDI-substrate mixed disulfides. These results suggest that the modulation of pK(a) of the C-terminal active cysteine by the movement of the side chain of these arginine residues into the active-site locales has evolved to allow PDI to efficiently catalyze both oxidation and isomerization reactions.
机译：蛋白质二硫键异构酶（PDI）在内质网中二硫键的形成中起着核心作用。它涉及二硫键的形成以及二硫键的还原和异构化。要成为所有三个反应的有效催化剂，需要复杂的机制。这些包括调节PDI活性位点半胱氨酸的pK（a）值的机制。在这里，我们检查了精氨酸120在调节这些半胱氨酸的pK（a）值中的作用。我们发现精氨酸120在调节PDI域中的C末端活性位半胱氨酸的pK（a）中起着重要作用，而在确定N末端活性位半胱氨酸的反应性中起着重要作用通过直接调制其pK（a）。在a'域中精氨酸120和相应残基精氨酸461的突变严重降低了PDI催化二硫键形成和还原的能力，但由于形成了更稳定的PDI-底物混合而增强了催化二硫键异构化的能力二硫化物。这些结果表明，通过这些精氨酸残基的侧链向活性位点的运动，对C-末端活性半胱氨酸的pK（a）进行了调节，从而使PDI有效地催化了氧化和异构化反应。

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