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首页> 外文期刊>Biochemistry >Mechanism of the Calcium-Induced trans−cis Isomerization of a Non-Prolyl Peptide Bond in Clostridium histolyticum Collagenase
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Mechanism of the Calcium-Induced trans−cis Isomerization of a Non-Prolyl Peptide Bond in Clostridium histolyticum Collagenase

机译：钙诱导溶组织梭状芽孢杆菌胶原酶中非脯氨酰肽键的反式顺式异构化机理

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摘要

cis peptide bonds in proteins are often rate-limiting steps in protein folding or conformationalnchange and are frequently stabilized bymetal ions. In the collagen-binding domain ofClostridiumhistolyticumncollagenase, the binding of calcium ions triggers the formation of a cis peptide bond. We present free energynsimulations of the formation of this cis peptide bond using a combined quantum mechanics/molecularnmechanics approach together with adaptive umbrella sampling. From these simulations, we have determinednthat the calcium ions not only stabilize the cis peptide bond thermodynamically but also catalyze itsnformation; the free energy barrier to the formation of the cis peptide bond decreases from 21.4 kcal/mol in thenabsence of calciumions to 10.3 kcal/mol in their presence. Two principal factors contribute to this reduction innthe energy barrier. The calcium ions electrostatically stabilize the lone pair on the nitrogen atom that formsnduring the isomerization. In addition, their attraction to acidic amino acid side chains and formation of anhydrogen bond network constrain the peptide backbone in a way that makes it easier for the nitrogen tonpyramidalize. Factors that explain the observed cooperativity of calcium binding are discussed.
机译：蛋白质中的顺式肽键通常是蛋白质折叠或构象变化中的限速步骤，并经常被金属离子稳定。在Clostridiumhistolyticumncollagenase的胶原结合域中，钙离子的结合触发了顺式肽键的形成。我们提出了使用组合的量子力学/分子力学方法与自适应伞式采样相结合的方式，形成该顺式肽键的自由能模拟。通过这些模拟，我们确定钙离子不仅在热力学上稳定了顺式肽键，而且还催化了它的形成。形成顺式肽键的自由能垒从不存在钙离子时的21.4 kcal / mol降低到存在钙离子时的10.3 kcal / mol。有两个主要因素有助于减少能源壁垒。钙离子静电稳定形成异构化的氮原子上的孤对。另外，它们对酸性氨基酸侧链的吸引力和氢键网络的形成以使氮磺酰胺化更容易的方式约束了肽主链。讨论了解释观察到的钙结合的协同作用的因素。

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  • 来源
    《Biochemistry》 |2010年第25期|p.5314-5320|共7页
  • 作者

    Justin Spiriti and Arjan van der Vaart;

  • 作者单位

    Department of Chemistry and Biochemistry and Center for Biological Physics, Arizona State University, P.O. Box 871604,Tempe, Arizona 85287-1604, and §Department of Chemistry, University of South Florida, 4202 East Fowler Avenue,CHE 205, Tampa, Florida 33620;

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