Structure−Reactivity Relationships among Metallothionein Three-Metal Domains: Role of Non-Cysteine Amino Acid Residues in Lobster Metallothionein and Human Metallothionein-3
| ISSN: | 1520-510X 0020-1669 |
|---|---|
| DOI: | 10.1021/ic000485s |
| Přístupová URL adresa: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::411bc0104824f5e76373d525c85c0d25 https://doi.org/10.1021/ic000485s |
| Přírůstkové číslo: | edsair.doi.dedup.....411bc0104824f5e76373d525c85c0d25 |
| Autor: | Muñoz A, Shaw Cf rd, Petering Dh |
| Rok vydání: | 2000 |
| Předmět: |
Models
Molecular Steric effects Protein Conformation Stereochemistry Dimer Molecular Sequence Data Peptide Calorimetry Protein Structure Secondary Inorganic Chemistry chemistry.chemical_compound Computer Graphics Animals Humans Metallothionein Reactivity (chemistry) Amino Acid Sequence Cysteine Physical and Theoretical Chemistry Beta (finance) Nuclear Magnetic Resonance Biomolecular chemistry.chemical_classification Binding Sites Hydrogen Bonding Peptide Fragments Nephropidae Amino acid Kinetics chemistry Thermodynamics Rabbits |
| Zdroj: | Inorganic Chemistry. 39:6114-6123 |
| ISSN: | 1520-510X 0020-1669 |
| DOI: | 10.1021/ic000485s |
| Popis: | Metallothionein (MT) domains of different origins, exhibiting distinct, highly conserved cysteine positions, show differences in metal-cysteine coordination and reactivity. Lobster MT, which includes two Cd3S9 beta domains, was chosen as a basic model to study the structure-function relationship among the clusters. The possible influence of (1) the position of the cysteine residues and (2) the steric and electrostatic effects of neighboring amino acids on the folding and stability of MT clusters have been examined with the native lobster beta C and beta N domains, each having nine cysteines and binding three M2+ ions, and a modified domain beta C-->N, in which the cysteines of the C-terminal domain are relocated so they are spaced as in the N-terminal domain. Each has been synthesized and characterized by UV, CD, 113Cd NMR, and 1H NMR spectroscopies. The synthetic native domains (Cd3 beta C and Cd3 beta N) displayed spectroscopic properties, metal-binding affinities, and kinetic reactivity similar to those of the holo protein. In contrast, the modified Cd3 beta C-->N domain was unusually reactive and, in the presence of Chelex, a metal-ion chelating resin, was converted to a Cd5(beta C-->N)2 dimer. These differences in structure and reactivity demonstrate that the requirements for formation of a stable type-B, Cd3S9, beta cluster are more stringent than simply the sequential positions of the cysteines along the peptide chain and include specific interactions with neighboring amino acids. Molecular mechanics calculations suggest that changes of even a single amino acid in lobster Cd3 beta N toward lobster Cd3 beta C-->N or in mammalian MT1 or MT2 toward Cd3 beta-MT3 (GIF) can destabilize their structures. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|