Abstract

This core resource provides crystallographic and molecular modeling tools to assist in the design and analysis of candidate hemoglobin-based oxygen carriers. Core 1 will specifically support two research projects; Project 1: Recombinant hemoglobins as artificial oxygen carriers and Project 2: Intramolecularly cross-linked hemoglobins. Each of these projects requires detailed molecular modeling studies of proposed oxygen carriers to assess the potential for obtaining molecules with the appropriate oxygen affinity and properties. The three-dimensional structures of the oxy-, de-oxy-, and liganded forms of those molecules selected for further study will assess how the structure differs from human hemoglobin and the predicted structure. This information will assist in improving the design (or properties) of these proteins.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL048517-04
Application #
5213972
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1996
Total Cost
Indirect Cost

  Publications

Bucci, Enrico; Pucciarelli, Stefania; Angeletti, Mauro (2013) Free energy changes and components implicit in the MWC allosteric model for the cooperative oxygen binding of hemoglobin. Biochemistry 52:4149-56
Koehler, Raymond C; Fronticelli, Clara; Bucci, Enrico (2008) Insensitivity of cerebral oxygen transport to oxygen affinity of hemoglobin-based oxygen carriers. Biochim Biophys Acta 1784:1387-94
Rebel, Annette; Ulatowski, John A; Joung, Karena et al. (2002) Regional cerebral blood flow in cats with cross-linked hemoglobin transfusion during focal cerebral ischemia. Am J Physiol Heart Circ Physiol 282:H832-41
Arosio, Daniele; Kwansa, Herman E; Gering, Henry et al. (2002) Static and dynamic light scattering approach to the hydration of hemoglobin and its supertetramers in the presence of osmolites. Biopolymers 63:1-11
Fronticelli, Clara; Bobofchak, Kevin M; Karavitis, Michael et al. (2002) Introduction of a new regulatory mechanism into human hemoglobin. Biophys Chem 98:115-26
Gattoni, M; Piro, M C; Boffi, A et al. (2001) The heme-globin and dimerization equilibria of recombinant human hemoglobins carrying site-specific beta chains mutations. Arch Biochem Biophys 386:172-8
Fronticelli, C; Arosio, D; Bobofchak, K M et al. (2001) Molecular engineering of a polymer of tetrameric hemoglobins. Proteins 44:212-22
Piro, M C; Militello, V; Leone, M et al. (2001) Heme pocket disorder in myoglobin: reversal by acid-induced soft refolding. Biochemistry 40:11841-50
Kwansa, H E; Young, A D; Arosio, D et al. (2000) Adipyl crosslinked bovine hemoglobins as new models of allosteric systems. Proteins 39:166-9
Matheson, B; Razynska, A; Kwansa, H et al. (2000) Appearance of dissociable and cross-linked hemoglobins in the renal hilar lymph. J Lab Clin Med 135:459-64

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