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首页> 外文期刊>Biochemistry >Allosteric Inhibition of FTP1B Activity by Selective Modification of a Non-Active Site Cysteine Residue
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Allosteric Inhibition of FTP1B Activity by Selective Modification of a Non-Active Site Cysteine Residue

机译：通过非活性位点半胱氨酸残基的选择性修饰对FTP1B活性的变构抑制。

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摘要

The fluorogenic reagent 4-(aminosulfonyl)-7-fluoro-2,l,3-benzoxadiazole (ABDF) attenuates the functional activity of the protein tyrosine phosphatase FTP1B by reacting selectively with a single cysteine residue,leaving other cysteines in the protein unmodified.This modification reduces V_(max) without substantially affecting substrate binding (K_m),indicative of an allosteric mode of inhibition.Consistent with this,the cysteine residue modified by ABDF,Cys 121,lies outside the catalytic site but makes interactions with residues that contact His 214,which has been shown to be important for catalysis.Cys 121 is highly conserved among phosphatases,and ABDF also inhibits TC-PTP and LAR.These findings illustrate that targeting cysteine residues outside catalytic sites may be exploited in allosterically regulating enzymes.Moreover,these results suggest a new strategy for inhibiting a promising diabetes target.
机译：荧光试剂4-（氨基磺酰基）-7-氟-2,1,3-苯并恶二唑（ABDF）通过选择性地与单个半胱氨酸残基反应而减弱了蛋白质酪氨酸磷酸酶FTP1B的功能活性，而使蛋白质中的其他半胱氨酸未修饰。该修饰降低了V_（max），而基本上不影响底物结合（K_m），表明变构抑制方式。与此相一致，ABDF修饰的半胱氨酸残基Cys 121位于催化位点之外，但与接触的残基相互作用已证明他的214对催化具有重要意义。Cys 121在磷酸酶中高度保守，ABDF也抑制TC-PTP和LAR。这些发现表明，针对催化位点以外的半胱氨酸残基可用于变构调节酶。这些结果提示了抑制有希望的糖尿病靶标的新策略。

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