title: The pH dependent Cu(II) and Zn(II) binding behavior of an analog methanobactin peptide.
abstract: The pH dependent reactivity of an analog methanobactin peptide (amb) with the sequence acetyl-His1-Cys2-Gly3-Pro4-His5-Cys6 (Mw = 694.79 Da) was investigated for its binding ability for a series of biologically active metal ions using ion mobility-mass spectrometry. Cu(II), Zn(II) and, to a lesser extent, Ni(II) were observed to form complexes with amb from 1 : 1 molar equivalent amb:metal(II) solutions at pH > 6, indicating the deprotonation of the imidazole N of His (pKa = 6.0) must occur to allow the initial anchoring of the metal(II) ion. The amb-metal(II) complexes were observed as both positive and negative ions, although the Zn(II) complexes preferred forming an overall negative ion complex which is consistent with the two thiolate groups of Cys2 and Cys6 being involved in Zn(II) coordination. The Cu(II) addition, however, always resulted in a Cys-Cys disulfide bridge in both Cu-free amb and Cu-bound amb, which excluded thiolate coordination to Cu(II). Collision cross- section measurements showed the Zn(II) and Cu(II) negative ion complexes were smaller than the positive ion complexes, suggesting Zn(II) binds most compactly via the imidazole N of His and the thiolate groups of Cys, whereas Cu(II) binds most compactly via the imidazole N of His and two deprotonated N of two amide groups on the peptide backbone. The lowest energy structures from the B3LYP/LanL2DZ level of theory showed the functional groups of His5, Cys2 and Cys6 coordinated to Zn(II), whereas the His1 and the amide nitrogens of Cys2 and Gly3 coordinated to Cu(II), producing an overall negative charged complex. The positive ion complexes of Zn(II) and Cu(II) were both shown to coordinate via the two imidazole nitrogens of His1 and His5 and either the oxygen of the backbone carbonyl of Cys6 or the oxygen of the C-terminal, respectively.
authors.affiliation: Department of Chemistry, Texas A&M University-Commerce, 2600 S Neal St, Commerce, Texas 75428, USA.
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Sesham
authors.affiliation: Department of Biology and Environmental Science, Texas A&M University-Commerce, 2600 S Neal St, Commerce, Texas 75428, USA.
authors.forename: Dongwon
authors.initials: D
authors.lastname: Choi
authors.affiliation: Department of Chemistry, Texas A&M University-Commerce, 2600 S Neal St, Commerce, Texas 75428, USA.
authors.forename: Anupama
authors.initials: A
authors.lastname: Balaji
authors.affiliation: Department of Chemistry, Texas A&M University-Commerce, 2600 S Neal St, Commerce, Texas 75428, USA.
authors.forename: Sahithi
authors.initials: S
authors.lastname: Cheruku
authors.affiliation: Department of Chemistry, Texas A&M University-Commerce, 2600 S Neal St, Commerce, Texas 75428, USA.
authors.forename: Chiranjeevi
authors.initials: C
authors.lastname: Ravichetti
authors.affiliation: Department of Chemistry, Texas A&M University-Commerce, 2600 S Neal St, Commerce, Texas 75428, USA.
authors.forename: Aisha A
authors.initials: AA
authors.lastname: Alsharani
authors.affiliation: Department of Chemistry, Texas A&M University-Commerce, 2600 S Neal St, Commerce, Texas 75428, USA.
authors.forename: Mahesbabu
authors.initials: M
authors.lastname: Nasani
authors.affiliation: Department of Chemistry, Texas A&M University-Commerce, 2600 S Neal St, Commerce, Texas 75428, USA.
authors.forename: Laurence A
authors.initials: LA
authors.lastname: Angel
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D003300:Copper / Q000737:chemistry / Q000378:metabolism*; D003545:Cysteine / Q000378:metabolism; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism; D006706:Homeostasis; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000378:metabolism*; D013058:Mass Spectrometry / Q000379:methods*; D020602:Methylosinus trichosporium / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D013329:Structure-Activity Relationship; D015032:Zinc / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D004220:Disulfides; D007093:Imidazoles; D009842:Oligopeptides; D010455:Peptides; C491147:methanobactin; D003300:Copper; D015032:Zinc; D003545:Cysteine