Structural analysis of the hemoglobin (Hb) system of Delphinus delphis revealed a high globin multiplicity: HPLC-electrospray ionization-mass spectrometry (ESI-MS) analysis evidenced three major beta (beta1 16,022 Da, beta2 16,036 Da, beta3 16,036 Da, labeled according to their progressive elution times) and two major alpha globins (alpha1 15,345 Da, alpha2 15,329 Da). ESI-tandem mass and nucleotide sequence analyses showed that beta2 globin differs from beta1 for the substitution Val126 --> Leu, while beta3 globin differs from beta2 for the isobaric substitution Lys65 --> Gln. The alpha2 globin differs from the alpha1 for the substitution Ser15 --> Ala. Anion-exchange chromatography allowed the separation of two Hb fractions and HPLC-ESI-MS analysis revealed that the fraction with higher pI (HbI) contained beta1, beta2 and both the alpha globins, and the fraction with lower pI (HbII) contained beta3 and both the alpha globins. Both D. delphis Hb fractions displayed a lower intrinsic oxygen affinity, a decreased effect of 2,3-BPG and a reduced cooperativity with respect to human HbA(0), with HbII showing the more pronounced differences. With respect to HbA(0), either the substitution Probeta5 --> Gly or the Probeta5 --> Ala is present in all the cetacean beta globins sequenced so far, and it has been hypothesized that position 5 of beta globins may have a role in the interaction with 2,3-BPG. Regarding the particularly lowered cooperativity of HbII, it is interesting to observe that the variant human HbA, characterized by the substitution Lysbeta65 --> Gln (HbJ-Cairo) has a decreased cooperativity with respect to HbA(0).
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s00360-009-0380-2 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The α-globin super-enhancer acts in an orientation-dependent manner.
Nat Commun
January 2025
Gene Regulation Laboratory, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, OX3 9DS, Oxford, UK.
Individual enhancers are defined as short genomic regulatory elements, bound by transcription factors, and able to activate cell-specific gene expression at a distance, in an orientation-independent manner. Within mammalian genomes, enhancer-like elements may be found individually or within clusters referred to as locus control regions or super-enhancers (SEs). While these behave similarly to individual enhancers with respect to cell specificity, distribution and distance, their orientation-dependence has not been formally tested.
View Article and Find Full Text PDFRelevance of Next-Generation Sequencing in the Diagnosis of Thalassemia and Hemoglobinopathies: The Experience of Four Italian Diagnostic Hubs.
Genes (Basel)
December 2024
Laboratory of Medical Genetics, Clinical Pathology UOC, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.
Unlabelled: Thalassemias and hemoglobinopathies are among the most common genetic diseases worldwide and have a significant impact on public health. The decreasing cost of next-generation sequencing (NGS) has quickly enabled the development of new assays that allow for the simultaneous analysis of small nucleotide variants (SNVs) and copy number variants (CNVs) as deletions/duplications of α- and β-globin genes.
Background/objectives: This study highlighted the efficacy and rapid identification of all types of mutations in the α- and β-globin genes, including silent variants, using the Devyser Thalassemia NGS kit.
Background: This study aimed to evaluate the efficacy of third-generation sequencing (TGS) and a thalassemia (Thal) gene diagnostic kit in identifying Thal gene mutations.
Methods: Blood samples (n = 119) with positive hematology screening results were tested using polymerase chain reaction (PCR)-based methods and TGS on the PacBio-Sequel-II-platform, respectively.
Results: Out of the 119 cases, 106 cases showed fully consistent results between the two methods, with TGS identified HBA1/2 and HBB gene mutations in 82 individuals.
[The impact and clinical implication of variants in the start codon of HBA gene on the phenotype of thalassemia].
Zhonghua Yi Xue Yi Chuan Xue Za Zhi
January 2025
Precision Medical Lab Center, People's Hospital of Yangjiang, Yangjiang, Guangdong 529500, China.
Objective: To analyze the correlation between variants in the start codon of the α-globin gene and phenotypes of thalassemia, so as to provide a basis for the diagnosis and prevention of α-thalassemia.
Methods: A retrospective study was conducted on 7 patients diagnosed by Yangjiang People's Hospital and Guangzhou Hybribio Co. Ltd.
Globin ferryl species: what is the nature of the protonation event at pH < 5?
J Biol Inorg Chem
December 2024
Department of Chemistry, Babes-Bolyai University, 11 Arany Janos Str., 400028, Cluj-Napoca, Romania.
The ferryl state in globins has previously been reported to undergo a protonation event below pH 5, as assessed using pH jump experiments with stopped-flow UV-Vis spectroscopy. This protonation entails hypsochromic shifts in the α and β bands (~ 20 to 40 nm) and an ~ 10 nm reduction in the energy difference between these two bands. We now report that in Mb this event is also characterized by a hypsochromic shift in the Soret band (~ 5 nm).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!