Computational Study of the Fe(CN)2CO Cofactor and Its Binding to HypC Protein

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• 作者：Marta Albareda ; Jose-Manuel Palacios ; Juan Imperial ; Luis F. Pacios
• 刊名：Journal of Physical Chemistry B
• 出版年：2013
• 出版时间：October 31, 2013
• 年：2013
• 卷：117
• 期：43
• 页码：13523-13533
• 全文大小：423K
• 年卷期：v.117,no.43(October 31, 2013)
• ISSN：1520-5207

文摘

In the intricate maturation process of [NiFe]-hydrogenases, the Fe(CN)₂CO cofactor is first assembled in a HypCD complex with iron coordinated by cysteines from both proteins and CO is added after ligation of cyanides. The small accessory protein HypC is known to play a role in delivering the cofactor needed for assembling the hydrogenase active site. However, the chemical nature of the Fe(CN)₂CO moiety and the stability of the cofactor鈥揌ypC complex are open questions. In this work, we address geometries, properties, and the nature of bonding of all chemical species involved in formation and binding of the cofactor by means of quantum calculations. We also study the influence of environmental effects and binding to cysteines on vibrational frequencies of stretching modes of CO and CN used to detect the presence of Fe(CN)₂CO. Carbon monoxide is found to be much more sensitive to sulfur binding and the polarity of the medium than cyanides. The stability of the HypC鈥揷ofactor complex is analyzed by means of molecular dynamics simulation of cofactor-free and cofactor-bound forms of HypC. The results show that HypC is stable enough to carry the cofactor, but since its binding cysteine is located at the N-terminal unstructured tail, it presents large motions in solution, which suggests the need for a guiding interaction to achieve delivery of the cofactor.