Hemoglobin Einstein: Semisynthetic deletion in the B‐helix of the α‐chain

Srinivasulu, Sonati; Manjula, Belur N.; Nagel, Ronald L.; Tsai, Ching Hsuan; Ho, Chien; Prabhakaran, M.; Acharya, Seetharama A.

doi:10.1110/ps.03567804

Cited by 4 publications

(1 citation statement)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…the tetrapeptide 23-26) from the B helix of the α chains [162]. Although natural Hb variants presenting even more extended deletions or insertions have been known [126], these have rarely been characterized in such detail as Hb Einstein, since they are uncommon and usually unstable.…”

Section: Molecular Surgery and Molecular Transplantationmentioning

confidence: 99%

The Allosteric Properties of Hemoglobin: Insights from Natural and Site Directed Mutants

Bellelli

Brunori

Miele³

et al. 2006

Current Protein and Peptide Science

View full text Add to dashboard Cite

After over a century of extensive research, hemoglobin has become the prototype of allosteric and cooperative proteins. Its molecular structure, known in great detail, has allowed the design of hundreds of site directed mutations, aimed at interfering with its function, and thus at testing our hypotheses on the molecular mechanisms of allostery. The wealth of information thus obtained is difficult to read except for specialists, not only because it makes use of many different technical approaches, but also because of its intrinsically patchy nature. Moreover, several researchers have tried to assign specific roles to segments of the polypeptide chains, rather than to single residues, and have tested their hypotheses by multiple point mutations or by complete replacement with the homologous segment from a different hemoglobin to produce chimeric macromolecules. This approach is in great need of a revision since putative functionally relevant segments partially overlap. This review briefly describes the structure and function of hemoglobin, and analyzes the effect of point mutations, multiple mutations and segment replacement, with special attention to possible biotechnological applications, ranging from pharmacology (Hb solutions as resuscitating fluids and sources of the protein found in hemoglobinopathies for biochemical studies) to bioreactors. Occasional reference is made to site directed mutants of myoglobin, whenever this helps clarifying perplexing results obtained on hemoglobin.

show abstract

Section: Molecular Surgery and Molecular Transplantationmentioning

confidence: 99%

The Allosteric Properties of Hemoglobin: Insights from Natural and Site Directed Mutants

Bellelli

Brunori

Miele³

et al. 2006

Current Protein and Peptide Science

View full text Add to dashboard Cite

show abstract

Pair-wise interactions of polymerization inhibitory contact site mutations of hemoglobin-S

et al. 2006

View full text Add to dashboard Cite

The linkage of pair-wise interactions of contact site mutations of HbS has been studied using Le Lamentin [His-20 (alpha)-->Gln], Hoshida [Glu-43 (beta)-->Gln] and alpha(2)beta (2) (T87Q) mutations as the prototype of three distinct classes of contact sites of deoxy HbS fiber. Binary mixture experiments established that beta(A)-chain with the Thr-87 (beta)-->Gln mutation is as potent as the gamma-chain of HbF (alpha(2)gamma(2)) in inhibiting polymerization. On combining the influence of Le Lamentin mutation with that of beta (2) (T87Q) mutations; the net influence is only partial additivity. On the other hand, in binary mixture studies, combined influence of Hoshida mutation with that of beta (2) (T87Q) mutations is synergistic. Besides, a significant level of synergistic complementation is also seen when the Le Lamentin and Hoshida mutations are combined in HbS (symmetrical tetramers). Le Lamentin and Hoshida mutation introduced into the cis-dimer of the asymmetric hybrid tetramer completely neutralizes the Val-6 (beta) dependent polymerization. Accordingly, we propose that combining the perturbation of intra-double strand contact site with that of an inter-double strand contact site exhibit synergy when they are present in two different chains of the alphabeta dimer. A comparison of the present results with that of the earlier studies suggest that when the two contact site perturbations are from the same sub-unit of the alphabeta dimer only partial additivity is observed. The map of interaction linkage of the contact site mutations exposes new strategies in the design of novel anti-sickling Hbs for the gene therapy of sickle cell disease.

show abstract

Sickle Cell Anaemia

Nagel

2006

Encyclopedia of Life Sciences

View full text Add to dashboard Cite

Sickle cell anaemia is a genetic disease, whose indispensable feature is the presence of a mutation in the beta globin gene that specifies one of the chains of haemoglobin. This mutation endows the haemoglobin with a new property: the capacity of polymerizing when deoxygenated. This mutation has several untoward consequences: haemolytic anaemia, acute chest syndrome, stroke, renal insufficiency, leg ulcers, osteonecrosis, etc. Lifespan is compromised and the only accepted treatment is hydroxyurea, which is capable of ameliorating the phenotype and extending the life of the patient.

show abstract

Hemoglobin Einstein: Semisynthetic deletion in the B‐helix of the α‐chain

Cited by 4 publications

References 43 publications

The Allosteric Properties of Hemoglobin: Insights from Natural and Site Directed Mutants

The Allosteric Properties of Hemoglobin: Insights from Natural and Site Directed Mutants

Pair-wise interactions of polymerization inhibitory contact site mutations of hemoglobin-S

Sickle Cell Anaemia

Contact Info

Product

Resources

About