Abstract

We plan to extend our initial studies on the stability of the glyceraldehyde adduct at the alpha- and the epsilon-NH2 groups of hemoglobin. These adducts are present as ketoamine adducts and it has become clear that those at the epsilon-NH2 groups of lysine residues are hydrolyzed much more rapidly than those at the alpha-NH2 groups. The effects of various buffers on this hydrolysis will also be studied. Studies with the 2-carbon aldehyde, glyceraldehyde, will be continued. When the initial Schiff base of this aldehyde and a protein rearrange to the ketoamine, a new aldehyde is generated and cross-linking occurs. Experiments designed to determine which adduct(s) of glyceraldehyde and hemoglobin contribute to the inhibition of gelation will be completed.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL018819-14
Application #
3335675
Study Section
(EH)
Project Start
1982-07-01
Project End
1987-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
14
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Rockefeller University
Department
Type
Graduate Schools
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

Manning, James M; Popowicz, Anthony M; Padovan, Julio C et al. (2012) Intrinsic regulation of hemoglobin expression by variable subunit interface strengths. FEBS J 279:361-9
Manning, Lois R; Popowicz, Anthony M; Padovan, Julio et al. (2010) Developmental expression of human hemoglobins mediated by maturation of their subunit interfaces. Protein Sci 19:1595-9
Manning, Lois R; Russell, J Eric; Popowicz, Anthony M et al. (2009) Energetic differences at the subunit interfaces of normal human hemoglobins correlate with their developmental profile. Biochemistry 48:7568-74
Manning, Lois R; Russell, J Eric; Padovan, Julio C et al. (2007) Human embryonic, fetal, and adult hemoglobins have different subunit interface strengths. Correlation with lifespan in the red cell. Protein Sci 16:1641-58
Ashiuchi, Makoto; Yagami, Takeshi; Willey, Ronald J et al. (2005) N-terminal acetylation and protonation of individual hemoglobin subunits: position-dependent effects on tetramer strength and cooperativity. Protein Sci 14:1458-71
Geva, Alon; Clark, Jennifer J; Zhang, Yuxun et al. (2004) Hemoglobin Jamaica plain--a sickling hemoglobin with reduced oxygen affinity. N Engl J Med 351:1532-8
Zhang, Yuxun; Manning, Lois R; Falcone, Jill et al. (2003) Human erythrocyte membrane band 3 protein influences hemoglobin cooperativity. Possible effect on oxygen transport. J Biol Chem 278:39565-71
Manning, L R; Manning, J M (2001) The acetylation state of human fetal hemoglobin modulates the strength of its subunit interactions: long-range effects and implications for histone interactions in the nucleosome. Biochemistry 40:1635-9
Chen, W; Dumoulin, A; Li, X et al. (2000) Transposing sequences between fetal and adult hemoglobins indicates which subunits and regulatory molecule interfaces are functionally related. Biochemistry 39:3774-81
Li, X; Himanen, J P; Martin de Llano, J J et al. (1999) Mutational analysis of sickle haemoglobin (Hb) gelation. Biotechnol Appl Biochem 29 ( Pt 2):165-84

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