Wide-Open Flaps Are Key to Urease Activity.

Substrate ingress and product egress from the active site of urease is tightly controlled by an active site flap. Molecular dynamics simulations of urease have revealed a previously unobserved wide-open flap state that, unlike the well-characterized closed and open states, allows ready access to the...

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Publicado en:Journal of the American Chemical Society Vol. 134; no. 24; pp. 9934 - 9938
Autores principales: Roberts, Benjamin P., Miller, III, Bill R., Roitberg, Adrian E., Kenneth M. Merz, Jr.
Formato: Artículo
Publicado: American Chemical Society 6/20/2012
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Acceso en línea:Ver este registro en EBSCOhost
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      dt: 6/20/2012
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        atl: Wide-Open Flaps Are Key to Urease Activity.
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          Roberts, Benjamin P.
          Miller, III, Bill R.
          Roitberg, Adrian E.
          Kenneth M. Merz, Jr.
        affil: Quantum Theory Project, University of Florida, P.O. Box 118435, Gainesville, Florida 32611-8435, United States
      su:
        Urease
        Binding sites
        Molecular dynamics
        Valence (Chemistry)
        Molecular structure
      sug:
        subj:
          Urease
          Binding sites
          Molecular dynamics
          Valence (Chemistry)
          Molecular structure
      ab: Substrate ingress and product egress from the active site of urease is tightly controlled by an active site flap. Molecular dynamics simulations of urease have revealed a previously unobserved wide-open flap state that, unlike the well-characterized closed and open states, allows ready access to the metal cluster in the active site. This state is easily reached from the open state via low free energy barriers. Additionally, we have found that even when the flap is closed, a region of the binding pocket is solvent-exposed, leading to the hypothesis that it may act as a substrate/product reservoir. The newly identified wide-open state offers further opportunities for small-molecule drug discovery by defining a more extensive active-site pocket than has been previously described.
      pubtype: Academic Journal
      doctype: Article
      src: R
    language: English
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