Functional Roles of a Structural Element Involving Na-π Interactions in the Catalytic Site of Ti Lipase Revealed by Molecular Dynamics Simulations.
Interactions between metal ions and π systems (metal-π interactions) are known to confer significant stabilization energy. However, in biological systems, few structures with metal-π coordination have been determined; thus, its roles must still be elucidated. The cation-π interactions are not correc...
| Publicado en: | Journal of the American Chemical Society Vol. 131; no. 46; pp. 16697 - 16705 |
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| Autores principales: | , , |
| Formato: | Artículo |
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American Chemical Society
11/25/2009
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| 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=46705218&site=ehost-live header: @attributes: shortDbName: hlh uiTerm: 46705218 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: 11/25/2009 vid: 131 iid: 46 pid: 997 pub: American Chemical Society artinfo: ui: 46705218 10.1021/ja903451b ppf: 16697 ppct: 8 formats: tig: atl: Functional Roles of a Structural Element Involving Na-π Interactions in the Catalytic Site of Ti Lipase Revealed by Molecular Dynamics Simulations. aug: au: Hagiwara, Yohsuke Matsumura, Hiroyoshi Tateno, Masaru affil: Center for Computational Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba Science City, Ibaraki 1 89-0001, Japan Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennodai 1-1-I, Tsukuba, Ibaraki 305-8571, Japan Department of Applied Chemistry, Graduate School of Engineering, Osaka Univeristy, Yamada-oka 2-1, Suita, Osaka 565-0871, Japan su: Metal ions Molecular dynamics Lipases Enthalpy Ligands (Chemistry) sug: subj: Metal ions Molecular dynamics Lipases Enthalpy Ligands (Chemistry) ab: Interactions between metal ions and π systems (metal-π interactions) are known to confer significant stabilization energy. However, in biological systems, few structures with metal-π coordination have been determined; thus, its roles must still be elucidated. The cation-π interactions are not correctly described by current molecular mechanics even when using a polarizable force field, and thus they require quantum mechanical calculations for accurate estimation. However, the huge computational costs of the latter methodologies prohibit long-time molecular dynamics (MD) simulations. Accordingly, we developed a novel scheme to obtain an effective potential for calculating the interaction energy with an accuracy comparable to that of advanced ab initio calculations at the CCSD(T) levels, and with computational costs comparable to those of conventional MM calculations. Then, to elucidate the functional roles of the Natphenylalanine (Phe) complex in the catalytic site of Ti lipase, we performed MD simulations in the presence! absence of the accurate Nat-π interaction energy. A comparison of these MD simulations revealed that a significantly large enthalpy gain in Na-Phe16 substantially stabilizes the catalytic site, whereas a water molecule could not be substituted for Na for sufficient stabilization energy. Thus, the cation-π interaction in the lipase establishes a remarkably stable core structure by combining a hydrophobic aromatic ring and hydrophilic residues, of which the latter form the catalytic triad, thereby contributing to large structural changes from the complex with ligands to the free form of the lipase. This is the first report to elucidate the detailed functional mechanisms of Nat-π interactions. pubtype: Academic Journal doctype: Article src: R language: English refInfo: copyright: @attributes: flag: Y dt: @attributes: year: 2009 holdings: @attributes: islocal: N |
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