title: Peptide-bound dinitrosyliron complexes (DNICs) and neutral/reduced-form Roussin's red esters (RREs/rRREs): understanding nitrosylation of [Fe-S] clusters leading to the formation of DNICs and RREs using a de novo design strategy.
abstract: This manuscript describes the interaction of low-molecular-weight DNICs with short peptides designed to explore the stability and structure of DNIC-peptide/RRE-peptide constructs. Although characterization of protein-bound and low-molecular-weight DNICs is possible via EPR, XAS, and NRVS, this study demonstrates that the combination of aqueous IR ν(NO) and UV-vis spectra can serve as an efficient tool to characterize and discriminate peptide-bound DNICs and RREs. The de novo chelate-cysteine-containing peptides KC(A)(n)CK-bound (n = 1-4) dinitrosyliron complexes KC(A)(n)CK-DNIC (CnA-DNIC) and monodentate-cysteine-containing peptides KCAAK-/KCAAHK-bound Roussin's red esters (RREs) KCAAK-RRE/KCAAHK-RRE were synthesized and characterized by aqueous IR, UV-vis, EPR, CD, XAS, and ESI-MS. In contrast to the inertness of chelate-cysteine-containing peptide-bound DNICs toward KCAAK/KCAAHK, transformation of KCAAK-RRE/KCAAHK-RRE into CnA-DNIC triggered by CnA and reversible transformation between CnA-DNIC and CnA-RRE via {Fe(NO)(2)}(9)-{Fe(NO)(2)}(10) reduced-form peptide-bound RREs demonstrate that the {Fe(NO)(2)}(9) motif displays a preference for chelate-cysteine-containing peptides over monodentate-cysteine-containing peptides. Also, this study may signify that nitrosylation of [Fe-S] proteins generating protein-bound RREs, reduced protein-bound RREs, or protein-bound DNICs are modulated by both the oxidation state of iron and the chelating effect of the bound proteins of [Fe-S] clusters.
authors.affiliation: Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan.
authors.forename: Zong-Sian
authors.initials: ZS
authors.lastname: Lin
authors.forename: Feng-Chun
authors.initials: FC
authors.lastname: Lo
authors.forename: Chih-Hsiang
authors.initials: CH
authors.lastname: Li
authors.forename: Chih-Hao
authors.initials: CH
authors.lastname: Chen
authors.forename: Wei-Ning
authors.initials: WN
authors.lastname: Huang
authors.forename: I-Jui
authors.initials: IJ
authors.lastname: Hsu
authors.forename: Jyh-Fu
authors.initials: JF
authors.lastname: Lee
authors.forename: Jia-Cherng
authors.initials: JC
authors.lastname: Horng
authors.forename: Wen-Feng
authors.initials: WF
authors.lastname: Liaw
mesh_terms: D000595:Amino Acid Sequence; D003545:Cysteine / Q000737:chemistry; D015195:Drug Design; D004952:Esters; D007501:Iron / Q000737:chemistry*; D007506:Iron-Sulfur Proteins / Q000737:chemistry; D009569:Nitric Oxide / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry*; D010084:Oxidation-Reduction; D010455:Peptides / Q000737:chemistry*; D012995:Solubility; D013455:Sulfur / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D004952:Esters; D007506:Iron-Sulfur Proteins; D009942:Organometallic Compounds; D010455:Peptides; D014867:Water; D009569:Nitric Oxide; D013455:Sulfur; D007501:Iron; D003545:Cysteine