title: Computational insight into nitration of human myoglobin.
abstract: Protein nitration is an important post-translational modification regulating protein structure and function, especially for heme proteins. Myoglobin (Mb) is an ideal protein model for investigating the structure and function relationship of heme proteins. With limited structural information available for nitrated heme proteins from experiments, we herein performed a molecular dynamics study of human Mb with successive nitration of Tyr103, Tyr146, Trp7 and Trp14. We made a detailed comparison of protein motions, intramolecular contacts and internal cavities of nitrated Mbs with that of native Mb. It showed that although nitration of both Tyr103 and Tyr146 slightly alters the local conformation of heme active site, further nitration of both Trp7 and Trp14 shifts helix A apart from the rest of protein, which results in altered internal cavities and forms a water channel, representing an initial stage of Mb unfolding. The computational study provides an insight into the nitration of heme proteins at an atomic level, which is valuable for understanding the structure and function relationship of heme proteins in non-native states by nitration.
authors.affiliation: School of Chemistry and Chemical Engineering, University of South China, Hengyang 421001, China; Laboratory of Protein Structure and Function, University of South China, Hengyang 421001, China. Electronic address: linlinying@hotmail.com.
authors.forename: Ying-Wu
authors.initials: YW
authors.lastname: Lin
authors.affiliation: School of Chemistry and Chemical Engineering, University of South China, Hengyang 421001, China.
authors.forename: Xiao-Gang
authors.initials: XG
authors.lastname: Shu
authors.affiliation: School of Chemistry and Chemical Engineering, University of South China, Hengyang 421001, China.
authors.forename: Ke-Jie
authors.initials: KJ
authors.lastname: Du
authors.affiliation: School of Chemistry and Chemical Engineering, University of South China, Hengyang 421001, China.
authors.forename: Chang-Ming
authors.initials: CM
authors.lastname: Nie
authors.affiliation: Laboratory of Protein Structure and Function, University of South China, Hengyang 421001, China.
authors.forename: Ge-Bo
authors.initials: GB
authors.lastname: Wen
mesh_terms: D020134:Catalytic Domain; D006418:Heme / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D056004:Molecular Dynamics Simulation; D009211:Myoglobin / Q000737:chemistry* / Q000378:metabolism; D009573:Nitrites / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D014364:Tryptophan / Q000737:chemistry / Q000378:metabolism; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism
chemical_list: D009211:Myoglobin; D009573:Nitrites; D014443:Tyrosine; D006418:Heme; D014364:Tryptophan
keywords: Heme active site; Heme proteins; Internal cavity; MD simulation; Nitration