A DFT/CDM Study of Metal-Carboxylate Interactions in Metalloproteins: Factors Governing the Maximum Number of Metal-Bound Carboxylates.
The number of negatively charged metal-bound Asp/GIu residues determines the net charge of the carboxylate-rich metal-binding site, which has been found to play a role in enhancing the affinity and/or selectivity of a protein cavity for a given metal cofactor. Therefore, it is of interest to know th...
| Publicado en: | Journal of the American Chemical Society Vol. 128; no. 5; pp. 1533 - 1562 |
|---|---|
| Autores principales: | , |
| Formato: | Artículo |
| Publicado: |
American Chemical Society
2/8/2006
|
| Materias: | |
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=hlh&AN=20074460&site=ehost-live header: @attributes: shortDbName: hlh uiTerm: 20074460 longDbName: Humanities International Complete uiTag: AN controlInfo: bkinfo: jinfo: jid: 00027863 ACS jtl: Journal of the American Chemical Society issn: 00027863 maglogo: N pubinfo: dt: 2/8/2006 vid: 128 iid: 5 pid: 997 pub: American Chemical Society artinfo: ui: 20074460 10.1021/ja055797e ppf: 1533 ppct: 29 formats: tig: atl: A DFT/CDM Study of Metal-Carboxylate Interactions in Metalloproteins: Factors Governing the Maximum Number of Metal-Bound Carboxylates. aug: au: Dudev, Todor Lim, Carmay affil: Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan. Department of Chemistry, National Tsing Hua University, Hsinchu 300, Taiwan. su: Metalloproteins Organometallic compounds Density functionals Proteins Ligands (Chemistry) Coordination compounds sug: subj: Metalloproteins Organometallic compounds Density functionals Proteins Ligands (Chemistry) Coordination compounds ab: The number of negatively charged metal-bound Asp/GIu residues determines the net charge of the carboxylate-rich metal-binding site, which has been found to play a role in enhancing the affinity and/or selectivity of a protein cavity for a given metal cofactor. Therefore, it is of interest to know the maximum number of carboxylates that could bind to a given metal (M) of charge q and the key factors determining this upper limit in protein cavities, which are usually relatively buried. Using density functional theory combined with the continuum dielectric method to compute the HO CHOOO exchange free energies, the maximum number of carboxylates bound to M in a relatively buried metal-binding site is found to depend on (i) the metal charge, q, (ii) the carboxylate-binding mode, and (iii) the first-shell carboxylate- second-shell ligand interactions. The maximum number of carboxylates bound to M in a fully/partially solvent inaccessible protein cavity would not likely exceed q + 2 if (a) the metal-bound Asp/Glu side chains are hydrogen bonded to a Lys/Arg side chain or several peptide backbone amides/Asn/Gln side chains in the metal's second coordination shell or (b) at least one acidic residue binds bidentately, as opposed to monodentately, to the metal cofactor. This number is reduced to q + 1 in the absence of stabilizing interactions from outer-shell ligand(s) and if all the carboxylates are bound monodentately to the metal cofactor in a buried cavity. The computational results are consistent with findings from a PDB survey of uni-, di-, and trivalent metal-binding sites containing Asp/GIu residues. pubtype: Academic Journal doctype: Article src: R language: English refInfo: copyright: @attributes: flag: Y dt: @attributes: year: 2006 holdings: @attributes: islocal: N |
|---|