Differential Effects of the Zn-His-Bkb vs Zn-His-[Asp/Glu] Triad on Zn-Core Stability and Reactivity.
The most common partner of the Zn-bound His is the Asp/Glu carboxylate side chain in catalytic Zn sites and the backbone (Bkb) carbonyl group in structural Zn sites. To elucidate the factors governing the selection of the second-shell partner of the Zn-bound His in structural/catalytic Zn sites, sys...
| Published in: | Journal of the American Chemical Society Vol. 127; no. 32; pp. 11336 - 11348 |
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| Main Authors: | , , |
| Format: | Article |
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American Chemical Society
8/17/2005
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=hlh&AN=18026736&site=ehost-live header: @attributes: shortDbName: hlh uiTerm: 18026736 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: 8/17/2005 vid: 127 iid: 32 pid: 997 pub: American Chemical Society artinfo: ui: 18026736 10.1021/ja051304u ppf: 11336 ppct: 12 formats: tig: atl: Differential Effects of the Zn-His-Bkb vs Zn-His-[Asp/Glu] Triad on Zn-Core Stability and Reactivity. aug: au: Yen-lin Lin Yu-ming Lee Carmay Lim affil: Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan R.O.C. Department of Chemistry, National Tsing Hua University, Hsinchu 300, Taiwan R.O.C. su: Zinc Particles (Nuclear physics) Density functionals Chemical reactions Research Fluids sug: subj: Zinc Particles (Nuclear physics) Density functionals Chemical reactions Research Fluids ab: The most common partner of the Zn-bound His is the Asp/Glu carboxylate side chain in catalytic Zn sites and the backbone (Bkb) carbonyl group in structural Zn sites. To elucidate the factors governing the selection of the second-shell partner of the Zn-bound His in structural/catalytic Zn sites, systematic studies using density functional theory and continuum dielectric calculations were performed to determine the relative contributions of the second-shell Bkb carbonyl and the Asp/Glu carboxylate to the Zn-core stability and reactivity. The results show that the contributions of the second-shell Bkb carbonyl and Asp/ Glu carboxylate to the Zn-core stability depend mainly on the solvent accessibility of the Zn-site and the composition of the Zn-core. They reveal the advantage of a second-shell Bkb carbonyl in anionic Zn cavities: it stabilizes anionic, buried Zn-cores more than the corresponding negatively charged Asp/Glu carboxylate, thus explaining the absence of the Zn-His-Asp/Glu triad in structural [Zn(Cys)(His)] cores. They also reveal the advantage of a second-shell Asp/Glu carboxylate in catalytic Zn-cores: relative to a Bkb carbonyl group, it increases (i) the HOMO energy of the cationic/neutral zinc core, (ii) the reactivity of the attacking Zn-bound OH, (iii) electron transfer to the substrate, and (iv) the stability of the metal complex upon electron transfer. Furthermore, a second-shell Asp/Glu carboxylate could facilitate product release in the common cationic catalytic cores, by acting as a proton acceptor of the Zn-bound His creating an Asp┅His dyad that stabilizes the zinc dication more than the respective Bkb┅His° dyad. pubtype: Academic Journal doctype: Article src: R language: English refInfo: copyright: @attributes: flag: Y dt: @attributes: year: 2005 holdings: @attributes: islocal: N |
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