5YZF

X-ray crystal structure of met K42C sperm whale myoglobin

Summary for 5YZF

• Entry DOI: 10.2210/pdb5yzf/pdb
• Descriptor: sperm whale myoglobin, PROTOPORPHYRIN IX CONTAINING FE (3 entities in total)
• Functional Keywords: myoglobin, oxygen transport
• Biological source: Physeter catodon
• Total number of polymer chains: 1
• Total formula weight: 17956.60

Authors

Yuan, H. (deposition date: 2017-12-14, release date: 2018-03-07, Last modification date: 2023-11-22)

Primary citation

Cheng, H.M.,Yuan, H.,Wang, X.J.,Xu, J.K.,Gao, S.Q.,Wen, G.B.,Tan, X.,Lin, Y.W.
Formation of Cys-heme cross-link in K42C myoglobin under reductive conditions with molecular oxygen
J. Inorg. Biochem., 182:141-149, 2018

PubMed Abstract: The structure and function of heme proteins are regulated by diverse post-translational modifications including heme-protein cross-links, with the underlying mechanisms not well understood. In this study, we introduced a Cys (K42C) close to the heme 4-vinyl group in sperm whale myoglobin (Mb) and solved its X-ray crystal structure. Interestingly, we found that K42C Mb can partially form a Cys-heme cross-link (termed K42C Mb-X) under dithiothreitol-induced reductive conditions in presence of O, as suggested by guanidine hydrochloride-induced unfolding and heme extraction studies. Mass spectrometry (MS) studies, together with trypsin digestion studies, further indicated that a thioether bond is formed between Cys42 and the heme 4-vinyl group with an additional mass of 16 Da, likely due to hydroxylation of the α‑carbon. We then proposed a plausible mechanism for the formation of the novel Cys-heme cross-link based on MS, kinetic UV-vis and electron paramagnetic resonance (EPR) studies. Moreover, the Cys-heme cross-link was shown to fine-tune the protein reactivity toward activation of HO. This study provides valuable insights into the post-translational modification of heme proteins, and also suggests that the Cys-heme cross-link can be induced to form in vitro, making it useful for design of new heme proteins with a non-dissociable heme and improved functions.

PubMed: 29477977
DOI: 10.1016/j.jinorgbio.2018.02.011

Experimental method

X-RAY DIFFRACTION (1.77 Å)