Abstract

Enter the text here that is the new abstract information for your application. This section must be no longer than 30 lines of text. Modified Specific Aims Section Enter the text here that is the new specific aims information for your application. One page is recommended. In view of a reduction of more than 25% from our requested budget, we would like to request a reduced level of effort on our grant. During the next two years, we would like to concentrate on Specific Aims #1 and #2 and to eliminate Specific Aim #3.

Public Health Relevance

Our research has provided definitive evidence that the simple two-structure model taught to al students of molecular biology, biochemistry, and biophysics fails to describe the essential mechanistic as well as structural and dynamic aspects of oxygen binding by hemoglobin. Our goal is to provide a new, more realistic description. In addition, the knowledge developed in this proposal will provide new insights for designing a new generation of hemoglobin-based oxygen carriers (blood substitutes) and resuscitation fluids for treatment of traumatic brain injury with hemorrhagic shock.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM084614-32A1
Application #
8368559
Study Section
Macromolecular Structure and Function A Study Section (MSFA)
Program Officer
Smith, Ward
Project Start
1979-05-01
Project End
2014-07-31
Budget Start
2012-09-30
Budget End
2013-07-31
Support Year
32
Fiscal Year
2012
Total Cost
$288,610
Indirect Cost
$98,610

  Institution

Name
Carnegie-Mellon University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
052184116
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213

  Publications

Lal, Jyotsana; Maccarini, Marco; Fouquet, Peter et al. (2017) Modulation of hemoglobin dynamics by an allosteric effector. Protein Sci 26:505-514
Tam, Ming F; Tam, Tsuey Chyi S; Simplaceanu, Virgil et al. (2015) Sickle Cell Hemoglobin with Mutation at ?His-50 Has Improved Solubility. J Biol Chem 290:21762-72
Yuan, Yue; Tam, Ming F; Simplaceanu, Virgil et al. (2015) New look at hemoglobin allostery. Chem Rev 115:1702-24
Yuan, Yue; Byrd, Catherine; Shen, Tong-Jian et al. (2013) Role of ?/?101Gln in regulating the effect of temperature and allosteric effectors on oxygen affinity in woolly mammoth hemoglobin. Biochemistry 52:8888-97
Fan, Jing-Song; Zheng, Yu; Choy, Wing-Yiu et al. (2013) Solution structure and dynamics of human hemoglobin in the carbonmonoxy form. Biochemistry 52:5809-20
Brillet, Thomas; Marden, Michael C; Yeh, Joanne I et al. (2012) Interaction of haptoglobin with hemoglobin octamers based on the mutation ?Asn78Cys or ?Gly83Cys. Am J Mol Biol 2:1-10
Yuan, Yue; Shen, Tong-Jian; Gupta, Priyamvada et al. (2011) A biochemical--biophysical study of hemoglobins from woolly mammoth, Asian elephant, and humans. Biochemistry 50:7350-60
Tiso, Mauro; Tejero, Jesús; Basu, Swati et al. (2011) Human neuroglobin functions as a redox-regulated nitrite reductase. J Biol Chem 286:18277-89
Makowski, L; Bardhan, J; Gore, D et al. (2011) WAXS studies of the structural diversity of hemoglobin in solution. J Mol Biol 408:909-21
Yuan, Yue; Simplaceanu, Virgil; Ho, Nancy T et al. (2010) An investigation of the distal histidyl hydrogen bonds in oxyhemoglobin: effects of temperature, pH, and inositol hexaphosphate. Biochemistry 49:10606-15

Showing the most recent 10 out of 15 publications