4LPI

A sperm whale myoglobin double mutant L29H/F43Y Mb with a distal hydrogen-bonding network

Summary for 4LPI

• Entry DOI: 10.2210/pdb4lpi/pdb
• Descriptor: Myoglobin, PROTOPORPHYRIN IX CONTAINING FE (3 entities in total)
• Functional Keywords: enzyme function initiative, distal heme hydrogen-bonding network, nitrite redutase, oxygen transport
• Biological source: Physeter catodon (Sperm whale)
• Total number of polymer chains: 1
• Total formula weight: 18023.62

Authors

Lin, Y. (deposition date: 2013-07-16, release date: 2014-07-16, Last modification date: 2023-11-08)

Primary citation

Yan, D.J.,Yuan, H.,Li, W.,Xiang, Y.,He, B.,Nie, C.M.,Wen, G.B.,Lin, Y.W.,Tan, X.
How a novel tyrosine-heme cross-link fine-tunes the structure and functions of heme proteins: a direct comparitive study of L29H/F43Y myoglobin
Dalton Trans, 44:18815-18822, 2015

PubMed Abstract: A heme-protein cross-link is a key post-translational modification (PTM) of heme proteins. Meanwhile, the structural and functional consequences of heme-protein cross-links are not fully understood, due to limited studies on a direct comparison of the same protein with and without the cross-link. A Tyr-heme cross-link with a C-O bond is a newly discovered PTM of heme proteins, and is spontaneously formed in F43Y myoglobin (Mb) between the Tyr hydroxyl group and the heme 4-vinyl group in vivo. In this study, we found that with an additional distal His29 introduced in the heme pocket, the double mutant L29H/F43Y Mb can form two distinct forms under different protein purification conditions, with and without a novel Tyr-heme cross-link. By solving the X-ray structures of both forms of L29H/F43Y Mb and performing spectroscopic studies, we made a direct structural and functional comparison in the same protein scaffold. It revealed that the Tyr-heme cross-link regulates the heme distal hydrogen-bonding network, and fine-tunes not only the spectroscopic and ligand binding properties, but also the protein reactivity. Moreover, the formation of the Tyr-heme cross-link in the double mutant L29H/F43Y Mb was investigated in vitro. This study addressed the key issue of how Tyr-heme cross-link fine-tunes the structure and functions of the heme protein, and provided a plausible mechanism for the formation of the newly discovered Tyr-heme cross-link.

PubMed: 26458300
DOI: 10.1039/c5dt03040d

Experimental method

X-RAY DIFFRACTION (1.36 Å)