Ligand binding to truncated hemoglobin N from Mycobacterium tuberculosis is strongly modulated by the interplay between the distal heme pocket residues and internal water (Articolo in rivista)

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Label
  • Ligand binding to truncated hemoglobin N from Mycobacterium tuberculosis is strongly modulated by the interplay between the distal heme pocket residues and internal water (Articolo in rivista) (literal)
Anno
  • 2008-01-01T00:00:00+01:00 (literal)
Alternative label
  • Ouellet, YH; Daigle, R; Lague, P; Dantsker, D; Milani, M; Bolognesi, M; Friedman, JM; Guertin, M (2008)
    Ligand binding to truncated hemoglobin N from Mycobacterium tuberculosis is strongly modulated by the interplay between the distal heme pocket residues and internal water
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Ouellet, YH; Daigle, R; Lague, P; Dantsker, D; Milani, M; Bolognesi, M; Friedman, JM; Guertin, M (literal)
Pagina inizio
  • 27270 (literal)
Pagina fine
  • 27278 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 283 (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • \"[Ouellet, Yannick H.; Daigle, Richard; Laguee, Patrick; Guertin, Michel] Univ Laval, Dept Biochem & Microbiol, Quebec City, PQ G1K 7P4, Canada; [Dantsker, David; Friedman, Joel M.] Albert Einstein Coll Med, Dept Physiol & Biophys, Bronx, NY 10461 USA; [Milani, Mario; Bolognesi, Martino] Univ Milan, Milano Res Unit, CNR, INFM, I-20131 Milan, Italy; [Milani, Mario; Bolognesi, Martino] Univ Milan, Dept Biomol Sci & Biotechnol, I-20131 Milan, Italy (literal)
Titolo
  • Ligand binding to truncated hemoglobin N from Mycobacterium tuberculosis is strongly modulated by the interplay between the distal heme pocket residues and internal water (literal)
Abstract
  • The survival of Mycobacterium tuberculosis requires detoxification of host center dot NO. Oxygenated Mycobacterium tuberculosis truncated hemoglobin N catalyzes the rapid oxidation of nitric oxide to innocuous nitrate with a second-order rate constant (k'NOD approximate to 745 x 10(6) M(-1 center dot)s(-1)), which is similar to 15-fold faster than the reaction of horse heart myoglobin. We ask what aspects of structure and/or dynamics give rise to this enhanced reactivity. A first step is to expose what controls ligand/substrate binding to the heme. We present evidence that the main barrier to ligand binding to deoxy-truncated hemoglobin N (deoxy-trHbN) is the displacement of a distal cavity water molecule, which is mainly stabilized by residue Tyr(B10) but not coordinated to the heme iron. As observed in the Tyr( B10)/Gln(E11) apolar mutants, once this kinetic barrier is lowered, CO and O-2 binding is very rapid with rates approaching 1 - 2 x 10(9) M(-1 center dot)s(-1). These large values almost certainly represent the upper limit for ligand binding to a heme protein and also indicate that the iron atom in trHbN is highly reactive. Kinetic measurements on the photoproduct of the center dot NO derivative of met-trHbN, where both the center dot NO and water can be directly followed, revealed that water rebinding is quite fast (similar to 1.49 x 10(8) s(-1)) and is responsible for the low geminate yield in trHbN. Molecular dynamics simulations, performed with trHbN and its distal mutants, indicated that in the absence of a distal water molecule, ligand access to the heme iron is not hindered. They also showed that a water molecule is stabilized next to the heme iron through hydrogen-bonding with Tyr(B10) and Gln(E11). (literal)
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