Abstract
Understanding the relationship between structure and function underpins both biochemistry and chemical biology, and has enabled the discovery of numerous agricultural and therapeutic agents. Small cysteine-rich proteins, which form a unique set of protein frameworks and folds, are found in all living organisms and often play crucial roles as hormones, growth factors, ion channel modulators and enzyme inhibitors in various biological pathways. Here we review secreted human cysteine-rich mini-proteins, classify them into broad families and briefly describe their structure and function. To systematically investigate this protein sub-class we designed a step-wise high throughput algorithm that is able to isolate the mature and active forms of human secreted cysteine-rich proteins (up to 200 amino acids in length) and extract their cysteine scaffolds. We limited our search to frameworks that contain an even number of cysteine residues (< 20), all of which are engaged in intra-molecular disulfide bonds. We found 53 different cysteine-rich frameworks spread over 378 secreted cysteine-rich mini-proteins. Restricting our search to those that contain >5% cysteine residues led to the identification of 22 cysteine-rich frameworks representing 21 protein families. Analysis of their molecular targets showed that these mini-proteins are frequently ligands for G protein- and enzyme-coupled receptors, transporters, extracellular enzyme inhibitors, and antimicrobial peptides. It is clear that these human secreted mini-proteins possess a wide diversity of frameworks and folds, some of which are conserved across the phylogenetic spectrum. Further study of these proteins will undoubtedly lead to insights into unresolved questions of basic biology, and the development of system-specific human therapeutics.
Keywords: Cysteine framework, cysteine scaffold, cysteine-rich peptides, cysteine-rich proteins, secreted human miniproteins, structure-function relationship, numerous agricultural and therapeutic agents, Small cysteine-rich proteins, protein frameworks, living organisms, growth factors, enzyme inhibitors, various biological pathways, antimicrobial peptides
Current Topics in Medicinal Chemistry
Title:Cysteine-Rich Mini-Proteins in Human Biology
Volume: 12 Issue: 14
Author(s): Vincent Lavergne, Ryan J. Taft and Paul F. Alewood
Affiliation:
Keywords: Cysteine framework, cysteine scaffold, cysteine-rich peptides, cysteine-rich proteins, secreted human miniproteins, structure-function relationship, numerous agricultural and therapeutic agents, Small cysteine-rich proteins, protein frameworks, living organisms, growth factors, enzyme inhibitors, various biological pathways, antimicrobial peptides
Abstract: Understanding the relationship between structure and function underpins both biochemistry and chemical biology, and has enabled the discovery of numerous agricultural and therapeutic agents. Small cysteine-rich proteins, which form a unique set of protein frameworks and folds, are found in all living organisms and often play crucial roles as hormones, growth factors, ion channel modulators and enzyme inhibitors in various biological pathways. Here we review secreted human cysteine-rich mini-proteins, classify them into broad families and briefly describe their structure and function. To systematically investigate this protein sub-class we designed a step-wise high throughput algorithm that is able to isolate the mature and active forms of human secreted cysteine-rich proteins (up to 200 amino acids in length) and extract their cysteine scaffolds. We limited our search to frameworks that contain an even number of cysteine residues (< 20), all of which are engaged in intra-molecular disulfide bonds. We found 53 different cysteine-rich frameworks spread over 378 secreted cysteine-rich mini-proteins. Restricting our search to those that contain >5% cysteine residues led to the identification of 22 cysteine-rich frameworks representing 21 protein families. Analysis of their molecular targets showed that these mini-proteins are frequently ligands for G protein- and enzyme-coupled receptors, transporters, extracellular enzyme inhibitors, and antimicrobial peptides. It is clear that these human secreted mini-proteins possess a wide diversity of frameworks and folds, some of which are conserved across the phylogenetic spectrum. Further study of these proteins will undoubtedly lead to insights into unresolved questions of basic biology, and the development of system-specific human therapeutics.
Export Options
About this article
Cite this article as:
Lavergne Vincent, J. Taft Ryan and F. Alewood Paul, Cysteine-Rich Mini-Proteins in Human Biology, Current Topics in Medicinal Chemistry 2012; 12 (14) . https://dx.doi.org/10.2174/156802612802652411
DOI https://dx.doi.org/10.2174/156802612802652411 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
- 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
- Announcements
Related Articles
-
The “Parkinsonian Heart”: From Novel Vistas to Advanced Therapeutic Approaches in Parkinsons Disease
Current Medicinal Chemistry Anesthetic Pharmacology and Perioperative Considerations for Heart Transplantation
Current Clinical Pharmacology Influence of the Bystander Effect on HSV-tk / GCV Gene Therapy. A Review.
Current Gene Therapy Hypotensive Effect of Hydroalcoholic Ziziphus jujuba Extract on Normotensive Rats
Current Nutrition & Food Science Design, Synthesis and Biological Evaluation of Benzopyran Derivatives as KATP Channel Openers
Letters in Drug Design & Discovery Stevia as a Natural Sweetener: A Review
Cardiovascular & Hematological Agents in Medicinal Chemistry Drug Therapy of Neuropathic Pain: Current Developments and Future Perspectives
Current Drug Targets Use of Non-steroidal Anti-inflammatory Drugs in Pregnancy: Impact on the Fetus and Newborn
Current Drug Metabolism New-Generation, Non-SSRI Antidepressants: Therapeutic Drug Monitoring and Pharmacological Interactions. Part 1: SNRIs, SMSs, SARIs
Current Medicinal Chemistry Pathophysiological Roles of Renin-Angiotensin System on Erythropoietic Action
Current Hypertension Reviews Long-Term Multimodal Therapy (Verapamil Associated with Propolis, Blueberry, Vitamin E and Local Diclofenac) on Patients with Peyronie's Disease (Chronic Inflammation of the Tunica Albuginea). Results of a Controlled Study
Inflammation & Allergy - Drug Targets (Discontinued) Potential Effect of Angiotensin II Receptor Blockade in Adipose Tissue and Bone
Current Pharmaceutical Design Risk Stratification in Pulmonary Embolism
Current Respiratory Medicine Reviews Involvement of Hypoxia-Inducible Factors in the Dysregulation of Oxygen Homeostasis in Sepsis
Cardiovascular & Hematological Disorders-Drug Targets Activated Protein C and Acute Kidney Injury: Selective Targeting of PAR-1
Current Drug Targets Renin-Angiotensin-Aldosterone System: A Current Drug Target for the Management of Neuropathic Pain
Current Drug Targets The Relevance of Drug Volume of Distribution in Antibiotic Dosing
Current Pharmaceutical Biotechnology Early Cerebral Infarction Following Aneurysmal Subarachnoid Hemorrhage: Frequency, Risk Factors, Patterns, and Prognosis
Current Neurovascular Research Ganoderma lucidum: A Potent Pharmacological Macrofungus
Current Pharmaceutical Biotechnology Hydrolyzates of Silkworm Pupae (Bombyx Mori) Protein is a New Source of Angiotensin I-Converting Enzyme Inhibitory Peptides(ACEIP)
Current Pharmaceutical Biotechnology