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W F Moo-Penn

Publications and source records attributed to W F Moo-Penn.

At least 37 records · Page 2Linked to original sources
PubMed1984

Structural and functional studies of hemoglobin Wayne: an elongated alpha-chain variant.

Hemoglobin Wayne (Hb Wayne) is a frame-shift, elongated alpha-chain variant that exists in two forms, with either asparagine or aspartic acid as residue 139. Oxygen equilibrium studies showed that stripped Hb Wayne Asn and Hb Wayne Asp possessed high oxygen affinity (P 1/2 = 0.60 and 0.23 mmHg at pH 7, respectively), were non-co-operative and have a markedly reduced Bohr effect (-delta log P 1/2/pH (7 to 8) = 0.34 and 0.10, respectively). Adding organic phosphate results in a decreased oxygen affinity and increased Bohr effect for both Hbs Wayne. The overall rate of carbon monoxide binding at pH 7 (l' = 5.6 X 10(6) M-1 S-1) was similar for both stripped Hbs Wayne and was 25-fold more rapid than that of stripped Hb A. When organic phosphate was added, Hb Wayne Asn exhibited a homogeneous slower rate of carbon monoxide binding (l' = 2.6 X 10(6) M-1 S-1), whereas Hb Wayne Asp showed heterogeneous binding (l' = 6.1 X 10(6) and 2.6 X 10(6) M-1 S-1 for fast and slow phases, respectively). The rates of overall oxygen dissociation and oxygen dissociation with carbon monoxide replacement for both Hbs Wayne were found to be slow compared to Hb A and uniquely different from each other. Similarly, sedimentation velocity experiments indicated that, although Hb Wayne Asn and Hb Wayne Asp were both less tetrameric than Hb A, each hemoglobin exhibited a distinct degree of oxygen-linked subunit dissociation. These observed differences in the allosteric properties of Hb Wayne Asn and Hb Wayne Asp appeared to be directly attributable to residue 139. The equilibrium and kinetic data are consistent with the X-ray diffraction analysis of Hb Wayne Asp, which shows that the C terminus of the deoxytetramers are severely disordered, a condition that results in major destabilization of the T conformation and disruption of normal hemoglobin function.

Amino Acid Sequence↗
PubMed1984

Hemoglobin Shelby [beta 131(H9) Gln----Lys] a correction to the structure of hemoglobin Deaconess and hemoglobin Leslie.

Hemoglobin Shelby, detected in two unrelated black families, has an electrophoretic mobility like Hb F on cellulose acetate (pH 8.4) and a mobility between Hbs S and C on citrate agar (pH 6.2). Globin chain analysis in acid and alkaline buffers revealed an abnormal chain migrating between beta A and beta S. Tests for unstable hemoglobins were positive. Hematologic data on both families indicated carriers have mild anemia. The variant showed a slightly lower affinity for oxygen with normal cooperativity and Bohr effect, and its reactions with 2,3-diphosphoglycerate and inositol hexaphosphate were similar to those of Hb A. Sequence analysis indicated the substitution of lysine for glutamine at position 131 in the beta-chain. In a previous report (1) we described a variant, Hb Deaconess, in which this residue was deleted. On reexamination of the data, we find that Hb Deaconess is identical to Hb Shelby.

Adolescent↗
PubMed1983

Hemoglobin Evanston: alpha 14(A12) Trp leads to Arg. A variant hemoglobin associated with alpha-thalassemia-2.

Hb Evanston (alpha 14 Trp leads to Arg) was detected on cellulose acetate at pH 8.4 as a band with an electrophoretic mobility similar to that of Hb S. In addition, a band migrating cathodic to Hb A2 suggested the presence of a variant Hb A2 with a substitution in the alpha-chain, a fact that was later confirmed by structural analysis. An unusual feature of Hb Evanston is its low percentage; less than 10% occurs in the hemolysate. Studies indicate that the variant is not unstable, but there appears to be a defect in globin-chain synthesis. Gene mapping also shows that it is associated with the alpha-thalassemia-2 gene. The variant has high oxygen affinity with normal cooperativity and a normal Bohr effect. The combination of Hb Evanston with alpha-thalassemia-2 produced anemia in this black family.

Female↗
PubMed1983

Hemoglobin Cheverly: an unstable hemoglobin associated with chronic mild anemia.

The evaluation of a family with chronic mild anemia led to the identification of a new unstable hemoglobin (Hemoglobin Cheverly). Modest anemia and reticulocytosis, normal to slightly increased mean corpuscular volume (MCV), and normal mean corpuscular hemoglobin concentration (MCHC) were present in the affected family members. Electrophoresis of blood samples on cellulose acetate and on citrate agar revealed normal patterns. Globin chain analysis and isoelectric focusing data were also normal. After incubation for 3 h at 41 degrees C, Heinz bodies were detected in 95-100% of erythrocytes from affected individuals. Positive heat and isopropanol tests confirmed the initial observation of the Heinz body preparation and indicated that an unstable hemoglobin was present. Structural analysis showed an amino acid substitution of Phe-Ser at position 45 (CD4) in the beta chain. Hemoglobin Cheverly has a reduced affinity for oxygen and a reduced Bohr effect, properties that can be rationalized on the basis of the x-ray crystallographic structure of normal hemoglobin. Despite structural and functional similarities between Hb Cheverly and Hb Hammersmith, beta 42 (CD1) Phe-Ser, the clinical manifestations of Hb Cheverly are mild in contrast to the severe disease observed with Hb Hammersmith. Reasons for the apparently silent clinical expression of Hb Cheverly are not known. We discuss the implications of unstable hemoglobins in the evaluation of chronic anemia in pediatric patients.

Anemia↗
PubMed1982

Hemoglobin Queens: alpha 34 (B15) Leu-Arg structural and functional properties and its association with Hb E.

Hemoglobin Queens: alpha 34 (B15) Leu-Arg was found in association with Hb E in a Vietnamese boy. The observed microcytosis and hypochromia were due to Hb E, which also occurred in other members of this family. The functional properties of Hb Queens in the absence and presence of allosteric effectors were normal. The abnormal hemoglobins appear to be unrelated to the hyperbilirubinemia that was observed at birth.

Amino Acids↗
PubMed1981

Hemoglobin connecticut (beta 21 (B3) Asp leads to Gly): a hemoglobin variant with low oxygen affinity.

Electrophoretic analysis of a hemolysate from a young man undergoing a routine physical examination revealed an abnormal hemoglobin with a mobility similar to Hb S on cellulose acetate (pH, 8.4). This new variant, designated Hb Connecticut, was found in three generations of a family of Polish descent. Several individuals possessing the variant exhibited mild anemia. Structural analysis of the abnormal beta-chain indicated that the amino acid substitution was at position 21 (B3), and involved the replacement of aspartic acid with glycine. Oxygen dissociation studies revealed low oxygen affinity. The alkaline Bohr effect and the degree of cooperativity were unchanged. Analysis of the crystal structure of the variant suggested that the low oxygen affinity was due to the possible disruption of salt bridges between aspartic acid 21(B3) and lysines 61(ES) and 65(E9), changes that could lead to steric interference in oxygen binding.

Adolescent↗
PubMed1981

Hemoglobin Cubujuqui (alpha 141 Arg-Ser): functional consequences of the alteration of the C-terminus of the alpha chain of hemoglobin.

Hemoglobin Cubujuqui (1) was detected in several members of a Mexican-American family. Structural analysis of this hemoglobin indicated that the carboxyl terminal arginine at position 141 in the alpha chain had been replaced by serine. This residue is critical not only in stabilizing the deoxy or T conformation by electrostatic interactions, but it is also involved in the Bohr effect through its linkage with Val 1 alpha of the opposite alpha chain in the tetramer. The variant exhibits high affinity for oxygen that is associated with destabilization of the deoxy conformation, and reduced cooperativity. The pH and the chloride sensitivity of the variant are also reduced, as compared to Hb A.

Amino Acid Sequence↗
PubMed1980

Hemoglobin Tampa:beta 79 (EF3) aspartic acid replaced by tyrosine.

Hemoglobin Tampa was detected in a 6-year-old male caucasian who is homozygous for this variant hemoglobin. The variant hemoglobin has an electrophoretic mobility between Hb F and Hb S on cellulose acetate (pH 8.5) and a mobility between Hb S and Hb C on citrate agar (pH 6.0). In acid buffer globin chain analysis revealed an abnormal beta chain with a mobility between the beta A and beta S chains, and in alkaline buffer the mobility of the chain was at the beta S position. Structural characterization of the variant beta chain indicates that aspartic acid is replaced with tyrosine at position 79, the site of a previously reported mutation, Asp replaced by Gly (Hb Hsi-Tsou). The clinical histories of the available family members including the homozygous propositus appear to be unremarkable.

Amino Acids↗
PubMed1980

Isolation of anticoagulant proteins from cobra venom (Naja nigricollis). Identity with phospholipases A2.

Three anticoagulant proteins were isolated from the venom of Naja nigricollis (spitting cobra). The peaks of anticoagulant activity co-chromatographed with phospholipase A2 activities. The three proteins were homogeneous by the criteria of electrophoresis in two acidic polyacrylamide gel systems. Electrophoresis in sodium dodecyl sulfate also yielded single protein bands with molecular weights of about 15,000. The amino acid compositions of the three anticoagulant proteins are reported. All three proteins have only one amino acid replacement in the first 25 to 30 amino acids of their NH2-terminal sequences, compared to the sequence of the basic phospholipase from N. nigricollis venom. Removal of Ca2+ from the crude venom caused loss of both anticoagulant and phospholipase activities, and restoration of Ca2+ caused partial recovery of both activities. Both activities were lost in parallel when the venom was heated between pH 6.0 and 8.5. The association of the anticoagulant effect with phospholipase activity contradicts the previous conclusion that phospholipase is not responsible for the anticoagulant action of cobra venom. The previous results might be explained by independence of the anticoagulant and phospholipase effects within the same protein molecule, or by different activity levels of monomer and dimer forms of the enzyme.

Amino Acid Sequence↗
PubMed1980

Hemoglobin variants and methods used for their characterization during 7 years of screening at the Center for Disease Control.

During 7 years of screening for hemoglobin variants, over 75 rare variants have been characterized. Of these, 18 were described for the first time. This report presents tabulated data regarding the structural and functional defects that were observed, information on the ethnic origin, and other special properties exhibited by these variants. The strategy and procedures for characterizing these variants are also summarized.

Centers for Disease Control and Prevention, U.S.↗
PubMed1980

Hemoglobin Ohio (beta 142 Ala replaced by): a new abnormal hemoglobin with high oxygen affinity and erythrocytosis.

Hemoglobin Ohio [beta 142 (H20) Ala replaced by Asp] was found in three members of a white family, all of whom showed erythrocytosis. The variant hemoglobin has a high oxygen affinity, a reduced Bohr effect, and diminished cooperativity. The functional abnormalities of Hb Ohio are explained by the proximity of the substituent beta 142 residue, both to beta 143 His, which is involved in the DPG binding site of hemoglobin, and to the critical C terminal region of the beta chain, which participates in the stabilization of the deoxy (T) conformation.

Adult↗
PubMed1979

Hemoglobin Dunn: alpha 6 (A4) aspartic acid replaced by asparagine.

Hemoglobin Dunn, alpha 6 (A4) Asp leads to Asn was found in a 39-year-old black woman and her daughter. The hematological data on the propositus were normal and there were no apparent clinical or pathological findings associated with this abnormal hemoglobin. The structural characterization of this variant is described.

Adult↗
PubMed1978

Hemoglobin Detroit: beta95 (FG2) lysine leads to asparagine.

Hb Detroit is a mutant which migrates between Hb A and Hb J Baltimore on cellulose acetate (pH 8.5), and with Hb A on citrate agar (pH 6.0). Globin chain analyses in alkaline and acid buffers reveal an abnormal beta chain with a mobility between the betaA and betaJ Baltimore chains. Structural characterization of this abnormal chain shows that lysine at position 95 is replaced by asparagine. No hematological abnormalities could be attributed to the presence of the mutant, and the oxygen affinity properties of the stripped hemoglobin are similar to those of Hb A. The beta95 residue which is substituted in Hb Detroit and also in Hb N Baltimore ((beta95 Lys leads to Glu) does not appear to be in a critical functional area of the molecule.

Adult↗