• Decrease font size
  • Return font size to normal
  • Increase font size
U.S. Department of Health and Human Services

Scientific Publications by FDA Staff

  • Print
  • Share
  • E-mail

Search Publications



Starting Date

Ending Date

Order by

Entry Details

Biochim Biophys Acta 2010 Oct;1804(10):1988-95

Extreme differences between Hemoglobins I and II of the Clam Lucina pectinalis in their reactions with nitrite.

Bonaventura C, Henkens R, De Jesus-Bonilla W, Lopez-Garriga J, Jia Y, Alayash AI, Siburt CJ, Crumbliss AL


The clam Lucina pectinalis supports its symbiotic bacteria by H(2)S transport in the open and accessible heme pocket of Lucina Hb I and by O(2) transport in the narrow and crowded heme pocket of Lucina Hb II. Remarkably, air-equilibrated samples of Lucina Hb I were found to be more rapidly oxidized by nitrite than any previously studied Hb, while those of Lucina Hb II showed an unprecedented resistance to oxidation induced by nitrite. Nitrite-induced oxidation of Lucina Hb II was enabled only when O(2) was removed from its active site. Structural analysis revealed that O(2) "clams up" the active site by hydrogen bond formation to B10Tyr and other distal-side residues. Quaternary effects further restrict nitrite entry into the active site and stabilize the hydrogen-bonding network in oxygenated Lucina Hb II dimers. The dramatic differences in nitrite reactivities of the Lucina Hbs are not related to their O(2) affinities or anaerobic redox potentials, which were found to be similar, but are instead a result of differences in accessibility of nitrite to their active sites; i.e. these differences are due to a kinetic rather than thermodynamic effect. Comparative studies revealed heme accessibility to be a factor in human Hb oxidation by nitrite as well, as evidenced by variations of rates of nitrite-induced oxidation that do not correlate with R and T state differences and inhibition of oxidation rate in the presence of O(2). These results provide a dramatic illustration of how evolution of active sites with varied heme accessibility can moderate the rates of inner-sphere oxidative reactions of Hb and other heme proteins.

Category: Journal Article
PubMed ID: #20601225 DOI: 10.1016/j.bbapap.2010.06.016
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2011-10-04 Entry Last Modified: 2012-08-29