Abstract
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.
Keywords: Human hemoglobin, naturally occurring mutants, site directed mutants, cooperativity, allosteric core
Current Protein & Peptide Science
Title: The Allosteric Properties of Hemoglobin: Insights from Natural and Site Directed Mutants
Volume: 7 Issue: 1
Author(s): Andrea Bellelli, Maurizio Brunori, Adriana E. Miele, Gianna Panetta and Beatrice Vallone
Affiliation:
Keywords: Human hemoglobin, naturally occurring mutants, site directed mutants, cooperativity, allosteric core
Abstract: 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.
Export Options
About this article
Cite this article as:
Bellelli Andrea, Brunori Maurizio, Miele E. Adriana, Panetta Gianna and Vallone Beatrice, The Allosteric Properties of Hemoglobin: Insights from Natural and Site Directed Mutants, Current Protein & Peptide Science 2006; 7 (1) . https://dx.doi.org/10.2174/138920306775474121
DOI https://dx.doi.org/10.2174/138920306775474121 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
Call for Papers in Thematic Issues
Advancements in Proteomic and Peptidomic Approaches in Cancer Immunotherapy: Unveiling the Immune Microenvironment
The scope of this thematic issue centers on the integration of proteomic and peptidomic technologies into the field of cancer immunotherapy, with a particular emphasis on exploring the tumor immune microenvironment. This issue aims to gather contributions that illustrate the application of these advanced methodologies in unveiling the complex interplay ...read more
Nutrition and Metabolism in Musculoskeletal Diseases
The musculoskeletal system consists mainly of cartilage, bone, muscles, tendons, connective tissue and ligaments. Balanced metabolism is of vital importance for the homeostasis of the musculoskeletal system. A series of musculoskeletal diseases (for example, sarcopenia, osteoporosis) are resulted from the dysregulated metabolism of the musculoskeletal system. Furthermore, metabolic diseases (such ...read more
Protein Folding, Aggregation and Liquid-Liquid Phase Separation
Protein folding, misfolding and aggregation remain one of the main problems of interdisciplinary science not only because many questions are still open, but also because they are important from the point of view of practical application. Protein aggregation and formation of fibrillar structures, for example, is a hallmark of a ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Recent Advance in the Research of Flavonoids as Anticancer Agents
Mini-Reviews in Medicinal Chemistry Regulatory Mechanism miR-302a-3p/E2F1/SNHG3 Axis in Nerve Repair Post Cerebral Ischemic Stroke
Current Neurovascular Research Oxidative Stress and Endothelial Dysfunction: Say NO to Cigarette Smoking!
Current Pharmaceutical Design Calcium Level Controlling Activities of Novel Derivatives of Amlodipine,Riodipine and Cerebrocrast
Letters in Drug Design & Discovery Recent Advances in Development of GPR40 Modulators (FFA1/FFAR1): An Emerging Target for Type 2 Diabetes
Mini-Reviews in Medicinal Chemistry Stroke and Neuroinflamation: Role of Sexual Hormones
Current Pharmaceutical Design The Role of AGEs and AGE Inhibitors in Diabetic Cardiovascular Disease
Current Drug Targets Nutritional and Therapeutic Potential of Garlic and Onion (Allium sp.)
Current Nutrition & Food Science <i>Asteriscus graveolens</i> exhibits Antihypertensive Activity through Activation of Vascular KATP Channels Activation in Rats
Endocrine, Metabolic & Immune Disorders - Drug Targets Pharmaceutical Applications of the Benzylisoquinoline Alkaloids from Argemone mexicana L.
Current Topics in Medicinal Chemistry Non-Viral Gene Delivery Methods
Current Pharmaceutical Biotechnology Antioxidant and Anticholinesterase Activities of Some Dialkylamino Substituted 3-Hydroxyflavone Derivatives
Medicinal Chemistry Ca2+ Signalling in Damaged Endothelium: Do Connexin Hemichannels Aid in Filling the Gap?
Current Drug Therapy From CHD Susceptibility Genes to New Therapeutics
Current Pharmacogenomics The Delivery of Personalised, Precision Medicines <i>via</i> Synthetic Proteins
Drug Delivery Letters Biopharmaceutics, Pharmacokinetics and Pharmacodynamics of Antituberculosis Drugs
Current Medicinal Chemistry Bivalent Ligands Derived from Huperzine A as Acetylcholinesterase Inhibitors
Current Topics in Medicinal Chemistry A Survey on Synthesis Processes of Structured Materials for Biomedical Applications: Iron-based Magnetic Nanoparticles, Polymeric Materials and Polymerization Processes
Current Pharmaceutical Design New Technologies: Non-Hormonal Female Contraception
Current Women`s Health Reviews Budesonide and Phenethyl Isothiocyanate Attenuate DNA Damage in Bronchoalveolar Lavage Cells of Mice Exposed to Environmental Cigarette Smoke
Current Cancer Drug Targets