TY - JOUR
T1 - HB shelby [β131(h9)GLN→LYS] in association with HB s [β6(a3)GLU→VAL]
T2 - Characterization, stability, and effects on HB s polymerization
AU - Adachi, K.
AU - Surrey, S.
AU - Tamary, H.
AU - Kim, J.
AU - Eck, H. S.
AU - Rappaport, E.
AU - Ohene-Frempong, K.
N1 - Funding Information:
This research was supported in part by grants HL 32908 and P60 HL 38632 (Comprehensive Sickle Cell Center) from the National Institutes of Health. We thank members of the Nucleic AcidProtein Core at the Children's Hospital of Philadelphia for oligonucleotide syntheses, protein characterization, and automated DNA sequence analysis.
PY - 1993
Y1 - 1993
N2 - When first tested for abnormal hemoglobins, a 2-year-old boy, appeared to have Hb F, Hb S and Hb A2. Confirmatory testing revealed a β chain variant inherited from his father and βs from his mother. Analysis of tryptic peptides in conjunction with automated DNA sequence analysis showed that the variant hemoglobin was Hb Shelby [β131(H9)Gln→Lys (CAG→AAG)]. Heat and mechanical stabilities of various liganded Hb Shelby tetramers were compared to those of Hb A and Hb S. Oxy-Hb Shelby precipitated more readily than oxy-Hb A, but was much more stable than oxy-Hb S during mechanical agitation. In contrast, oxy-Hb Shelby was much less stable than oxy-Hb A and oxy-Hb S following heat treatment. Met-Hb Shelby was most unstable compared to other liganded forms of Hb Shelby, while deoxy- and carbonmonoxy-forms of Hb Shelby showed similar heat-induced precipitation rates. These data indicate that heat instability of Hb Shelby is accompanied by heme oxidation, and that denaturation by mechanical agitation occurs in the absence of heme oxidation. Hb Shelby, like Hb A, can form hybrids with Hb S which participate in polymer formation in vitro. However, Hb S/Hb Shelby hybrids copolymerized with Hb S less than A/S hybrids. Since the patient's MCHC value is normal, this finding coupled with the elevated Hb A2 and Hb F levels, both of which are known to inhibit polymerization of Hb S, may contribute to the patient's mild clinical presentation.
AB - When first tested for abnormal hemoglobins, a 2-year-old boy, appeared to have Hb F, Hb S and Hb A2. Confirmatory testing revealed a β chain variant inherited from his father and βs from his mother. Analysis of tryptic peptides in conjunction with automated DNA sequence analysis showed that the variant hemoglobin was Hb Shelby [β131(H9)Gln→Lys (CAG→AAG)]. Heat and mechanical stabilities of various liganded Hb Shelby tetramers were compared to those of Hb A and Hb S. Oxy-Hb Shelby precipitated more readily than oxy-Hb A, but was much more stable than oxy-Hb S during mechanical agitation. In contrast, oxy-Hb Shelby was much less stable than oxy-Hb A and oxy-Hb S following heat treatment. Met-Hb Shelby was most unstable compared to other liganded forms of Hb Shelby, while deoxy- and carbonmonoxy-forms of Hb Shelby showed similar heat-induced precipitation rates. These data indicate that heat instability of Hb Shelby is accompanied by heme oxidation, and that denaturation by mechanical agitation occurs in the absence of heme oxidation. Hb Shelby, like Hb A, can form hybrids with Hb S which participate in polymer formation in vitro. However, Hb S/Hb Shelby hybrids copolymerized with Hb S less than A/S hybrids. Since the patient's MCHC value is normal, this finding coupled with the elevated Hb A2 and Hb F levels, both of which are known to inhibit polymerization of Hb S, may contribute to the patient's mild clinical presentation.
UR - http://www.scopus.com/inward/record.url?scp=0027321286&partnerID=8YFLogxK
U2 - 10.3109/03630269308997486
DO - 10.3109/03630269308997486
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C2 - 8226094
AN - SCOPUS:0027321286
SN - 0363-0269
VL - 17
SP - 329
EP - 343
JO - Hemoglobin
JF - Hemoglobin
IS - 4
ER -