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.

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National Heart, Lung, and Blood Institute (NHLBI)
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Rockefeller University
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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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