Regulating the Coordination State of a Heme Protein by a Designed Distal Hydrogen‐Bonding Network

ChemistryOpen

Jun-Fang Du¹  Dr. Wei Li⁴  Prof.𠁝r. Lianzhi Li⁵  Prof.𠁝r. Ge-Bo Wen²  Prof.𠁝r. Ying-Wu Lin³ 

[1] School of Chemistry and Chemical Engineering, University of South China, Hengyang, (P. R. China;Laboratory of Protein Structure and Function, University of South China, Hengyang, (P. R. China;E-mail address: 关键词: crystal structures;    heme proteins;    hydrogen bonding;    non-native states;    protein design;   

DOI  :  10.1002/open.201402108

来源: Wiley

【 摘 要 】

Abstract

Heme coordination state determines the functional diversity of heme proteins. Using myoglobin as a model protein, we designed a distal hydrogen-bonding network by introducing both distal glutamic acid (Glu29) and histidine (His43) residues and regulated the heme into a bis-His coordination state with native ligands His64 and His93. This resembles the heme site in natural bis-His coordinated heme proteins such as cytoglobin and neuroglobin. A single mutation of L29E or F43H was found to form a distinct hydrogen-bonding network involving distal water molecules, instead of the bis-His heme coordination, which highlights the importance of the combination of multiple hydrogen-bonding interactions to regulate the heme coordination state. Kinetic studies further revealed that direct coordination of distal His64 to the heme iron negatively regulates fluoride binding and hydrogen peroxide activation by competing with the exogenous ligands. The new approach developed in this study can be generally applicable for fine-tuning the structure and function of heme proteins.

【 授权许可】

CC BY-NC-ND   
© 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.