4PQB

A sperm whale myoglobin double mutant L29E/F43H Mb with a non-native bis-His (His64/His93) coordination

Summary for 4PQB

• Entry DOI: 10.2210/pdb4pqb/pdb
• Related: 4IT8 4PQC
• Descriptor: Myoglobin, PROTOPORPHYRIN IX CONTAINING FE (3 entities in total)
• Functional Keywords: structural genomics, enzyme function initiative, alpha helix bundle, oxygen transport
• Biological source: Physeter catodon (Sperm whale)
• Total number of polymer chains: 1
• Total formula weight: 17989.57

Authors

Ying-wu, L.,Xiang-shi, T.,Wei, L. (deposition date: 2014-03-01, release date: 2015-01-14, Last modification date: 2023-09-20)

Primary citation

Du, J.F.,Li, W.,Li, L.,Wen, G.B.,Lin, Y.W.,Tan, X.
Regulating the coordination state of a heme protein by a designed distal hydrogen-bonding network.
ChemistryOpen, 4:97-101, 2015

PubMed 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.

PubMed: 25969804
DOI: 10.1002/open.201402108

Experimental method

X-RAY DIFFRACTION (1.942 Å)