PDBsum entry 4lpi

Oxygen transport

PDB id: 4lpi

Contents

Protein chain

153 a.a.

Ligands

HEM

Waters ×199

References listed in PDB file

Key reference

• Title: How a novel tyrosine-Heme cross-Link fine-Tunes the structure and functions of heme proteins: a direct comparitive study of l29h/f43y myoglobin.
• Authors: D.J.Yan, H.Yuan, W.Li, Y.Xiang, B.He, C.M.Nie, G.B.Wen, Y.W.Lin, X.Tan.
• Ref.: Dalton Trans, 2015, 44, 18815-18822. [DOI no: 10.1039/c5dt03040d]
• PubMed id: 26458300

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.