Samajdar Rudra N, Manogaran Dhivya, Yashonath S, Bhattacharyya Aninda J
Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore 560012, India.
Phys Chem Chem Phys. 2018 Apr 18;20(15):10018-10029. doi: 10.1039/c8cp00605a.
Quasi reversibility in electrochemical cycling between different oxidation states of iron is an often seen characteristic of iron containing heme proteins that bind dioxygen. Surprisingly, the system becomes fully reversible in the bare iron-porphyrin complex: hemin. This leads to the speculation that the polypeptide bulk (globin) around the iron-porphyrin active site in these heme proteins is probably responsible for the electrochemical quasi reversibility. To understand the effect of such polypeptide bulk on iron-porphyrin, we study the interaction of specific amino acids with the hemin center in solution. We choose three representative amino acids-histidine (a well-known iron coordinator in bio-inorganic systems), tryptophan (a well-known fluoroprobe for proteins), and cysteine (a redox-active organic molecule). The interactions of these amino acids with hemin are studied using electrochemistry, spectroscopy, and density functional theory. The results indicate that among these three, the interaction of histidine with the iron center is strongest. Further, histidine maintains the electrochemical reversibility of iron. On the other hand, tryptophan and cysteine interact weakly with the iron center but disturb the electrochemical reversibility by contributing their own redox active processes to the system. Put together, this study attempts to understand the molecular interactions that can control electrochemical reversibility in heme proteins. The results obtained here from the three representative amino acids can be scaled up to build a heme-amino acid interaction database that may predict the electrochemical properties of any protein with a defined polypeptide sequence.
铁在不同氧化态之间进行电化学循环时的准可逆性是含血红素且能结合双氧的蛋白质常见的特征。令人惊讶的是，在裸露的铁-卟啉配合物：血红素中，该体系变得完全可逆。这引发了一种推测，即这些血红素蛋白中铁-卟啉活性位点周围的多肽主体（球蛋白）可能是电化学准可逆性的原因。为了理解这种多肽主体对铁-卟啉的影响，我们研究了溶液中特定氨基酸与血红素中心的相互作用。我们选择了三种代表性氨基酸——组氨酸（生物无机体系中著名的铁配位体）、色氨酸（蛋白质中著名的荧光探针）和半胱氨酸（一种具有氧化还原活性的有机分子）。利用电化学、光谱学和密度泛函理论研究了这些氨基酸与血红素的相互作用。结果表明，在这三种氨基酸中，组氨酸与铁中心的相互作用最强。此外，组氨酸维持了铁的电化学可逆性。另一方面，色氨酸和半胱氨酸与铁中心的相互作用较弱，但通过将自身的氧化还原活性过程贡献给体系而干扰了电化学可逆性。综上所述，本研究试图理解能够控制血红素蛋白电化学可逆性的分子相互作用。从这三种代表性氨基酸获得的结果可以扩展以建立一个血红素-氨基酸相互作用数据库，该数据库可能预测具有确定多肽序列的任何蛋白质的电化学性质。
