锈铁氧化还原蛋白-细胞色素c4-细胞色素氧化酶三元复合物的分子模拟：对嗜铁氧化硫杆菌中可能的氢键介导识别和电子转移反应的洞察

Molecular modeling of the ternary complex of Rusticyanin-cytochrome c4-cytochrome oxidase: an insight to possible H-bond mediated recognition and electron transfer reaction in T. ferrooxidans.

作者信息

Mukhopadhyay B P, Ghosh B, Bairagya H R, Nandi T K, Chakrabarti B, Bera A K

机构信息

Department of Chemistry, National Institute of Technology, Durgapur-713209, West Bengal, India.

出版信息

J Biomol Struct Dyn. 2008 Apr;25(5):543-51. doi: 10.1080/07391102.2008.10507201.

DOI:10.1080/07391102.2008.10507201

PMID:18282009

Abstract

The metabolism of Thiobacillus ferrooxidans involves electron transfer from the Fe+2 ions in the extracellular environment to the terminal oxygen in the bacterial cytoplasm through a series of periplasmic proteins like Rusticyanin (RCy), Cytochrome (Cyt c4), and Cytochrome oxidase (CcO). The energy minimization and MD studies reveal the stabilization of the three redox proteins in their ternary complex through the direct and water mediated H-bonds and electrostatic interaction. The surface exposed polar residues of the three proteins, i.e., RCy (His 143, Thr 146, Lys 81, Glu 20), Cyt c4 (Asp 5, 15, 52, Ser 14, Glu 61), and CcO (Asp 135, Glu 126, 140, 142, Thr 177) formed the intermolecular hydrogen bonds and stabilized the ternary complex. The oxygen (Oepsilon1) of Glu 126, 140, and 142 on subunit II of the CcO interact to the exposed side-chain and Ob atoms of the Asp 52 of Cyt c4 and Glu 20 and Leu 12 of RCy. The Asp 135 of subunit II also forms H-bond with the Nepsilon atom of Lys 81 of RCy. The Oepsilon1 of Glu 61 of Cyt c4 is also H-bonded to Ogamma atom of Thr 177 of CcO. Solvation followed by MD studies of the ternary protein complex revealed the presence of seven water molecules in the interfacial region of the interacting proteins. Three of the seven water molecules (W 79, W 437, and W 606) bridged the three proteins by forming the hydrogen bonded network (with the distances approximately 2.10-2.95 A) between the Lys 81 (RCy), Glu 61 (Cyt c4), and Asp 135 (CcO). Another water molecule W 603 was H-bonded to Tyr 122 (CcO) and interconnected the Lys 81 (RCy) and Asp 135 (CcO) through the water molecules W 606 and W 437. The other two water molecules (W 21 and W 455) bridged the RCy to Cyt c4 through H-bonds, whereas the remaining W 76 interconnected the His 53 (Cytc4) to Glu 126 (CcO) with distances approximately 2.95-3.0 A.

摘要

氧化亚铁硫杆菌的代谢涉及电子从细胞外环境中的Fe²⁺离子通过一系列周质蛋白，如rusticyanin（RCy）、细胞色素（Cyt c4）和细胞色素氧化酶（CcO）转移到细菌细胞质中的末端氧。能量最小化和分子动力学研究表明，通过直接和水介导的氢键及静电相互作用，三种氧化还原蛋白在其三元复合物中得以稳定。这三种蛋白质表面暴露的极性残基，即RCy（His 143、Thr 146、Lys 81、Glu 20）、Cyt c4（Asp 5、15、52、Ser 14、Glu 61）和CcO（Asp 135、Glu 126、140、142、Thr 177）形成分子间氢键并稳定了三元复合物。CcO亚基II上的Glu 126、140和142的氧（Oε1）与Cyt c4的Asp 52以及RCy的Glu 20和Leu 12暴露的侧链和Oβ原子相互作用。亚基II的Asp 135也与RCy的Lys 81的Nε原子形成氢键。Cyt c4的Glu 61的Oε1也与CcO的Thr 177的Oγ原子形成氢键。对三元蛋白质复合物进行溶剂化处理并随后进行分子动力学研究，结果显示在相互作用蛋白质的界面区域存在七个水分子。七个水分子中的三个（W 79、W 437和W 606）通过在Lys 81（RCy）、Glu 61（Cyt c4）和Asp 135（CcO）之间形成氢键网络（距离约为2.10 - 2.95 Å）连接这三种蛋白质。另一个水分子W 603与Tyr 122（CcO）形成氢键，并通过水分子W 606和W 437将Lys 81（RCy）和Asp 135（CcO）相互连接。另外两个水分子（W 21和W 455）通过氢键将RCy与Cyt c4连接起来，而其余的W 76以约2.95 - 3.0 Å的距离将His 53（Cytc4）与Glu 126（CcO）连接起来。