Structural Classification of Small, Disulfide-rich Protein Domains

Cheek, Sara; Krishna, S. Sri; Grishin, Nick V.

doi:10.1016/j.jmb.2006.03.017

Cited by 89 publications

(86 citation statements)

References 89 publications

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“…The cysteine knot is a protein motif containing three disulfide bridges, where two disulfide bonds with their backbone form a loop through which a third disulfide bond passes. This motif is found in 40% of known disulfide rich proteins [38] and provides structural stability to the protein. Despite having similar overall topology, the cysteine knot toxins may show some local structural and dynamic differences.…”

Section: Structurementioning

confidence: 99%

Conotoxins: Structure, Therapeutic Potential and Pharmacological Applications

Mir¹,

Karim²,

Kamal³

et al. 2016

CPD

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Cone snails, also known as marine gastropods, from Conus genus produce in their venom a diverse range of small pharmacologically active structured peptides called conotoxins. The cone snail venoms are widely unexplored arsenal of toxins with therapeutic and pharmacological potential, making them a treasure trove of ligands and peptidic drug leads. Conotoxins are small disulphide bonded peptides which act as remarkable selective inhibitors and modulators of ion channels (calcium, sodium, potassium), nicotinic acetylcholine receptors, noradrenaline transporters, N-methyl-D-aspartate receptors, and neurotensin receptors. They are highly potent and specific against several neuronal targets making them valuable as research tools, drug leads and even therapeutics. In this review we discuss their gene superfamily classification, nomenclature, post-translational modification, structural framework, pharmacology and medical applications of the active conopeptides. We aim to give an overview of their structure and therapeutic potential. Understanding these aspects of conopeptides will help in designing more specific peptidic analogues.

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Section: Structurementioning

confidence: 99%

Conotoxins: Structure, Therapeutic Potential and Pharmacological Applications

Mir¹,

Karim²,

Kamal³

et al. 2016

CPD

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“…The disulfide threeͲdimensional structure is highly conserved in Nature and has been used for protein clustering (Cheek et al, 2006;Chuang et al, 2003;Harrison and Sternberg, 1996;Thangudu et al, 2007). Different schemes have been introduced to classify the disulfide conformers (Harrison and Sternberg, 1996;Hutchinson and Thornton, 1996;Ozhogina and Bominaar, 2009;Schmidt et al, 2006;Srinivasan et al, 1990) and in this work we adopted the scheme proposed by Schmidt et al (2006).…”

Section: Introductionmentioning

confidence: 99%

Conformational characterization of disulfide bonds: A tool for protein classification

Marques¹,

Fonseca²,

Drury³

et al. 2010

Journal of Theoretical Biology

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“…Small protein domains whose structural features are determined by their disulfide bonds are usually referred to as disulfide-rich domains (DRDs) (24). The group of proteins that is covered by this definition is broad, including both secreted and intracellular proteins, and they are involved in a wide variety of functions, such as growth factors, toxins, enzyme inhibitors, and structural or ligand-binding domains within larger polypeptides (24).…”

mentioning

confidence: 99%

“…The group of proteins that is covered by this definition is broad, including both secreted and intracellular proteins, and they are involved in a wide variety of functions, such as growth factors, toxins, enzyme inhibitors, and structural or ligand-binding domains within larger polypeptides (24). Since protein classification of small proteins is often unreliable using common sequence and structural comparison tools, Cheek et al undertook a classification of 2945 DRDs found in the PDB on the basis of their structural and evolutionary relatedness as well as disulfide bonding patterns.…”

mentioning

confidence: 99%

Association Between Foldability and Aggregation Propensity in Small Disulfide-Rich Proteins

Fraga

Graña-Montes²,

Illa³

et al. 2014

Antioxidants & Redox Signaling

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Aims: Disulfide-rich domains (DRDs) are small proteins whose native structure is stabilized by the presence of covalent disulfide bonds. These domains are versatile and can perform a wide range of functions. Many of these domains readily unfold on disulfide bond reduction, suggesting that in the absence of covalent bonding they might display significant disorder. Results: Here, we analyzed the degree of disorder in 97 domains representative of the different DRDs families and demonstrate that, in terms of sequence, many of them can be classified as intrinsically disordered proteins (IDPs) or contain predicted disordered regions. The analysis of the aggregation propensity of these domains indicates that, similar to IDPs, their sequences are more soluble and have less aggregating regions than those of other globular domains, suggesting that they might have evolved to avoid aggregation after protein synthesis and before they can attain its compact and covalently linked native structure. Innovation and Conclusion: DRDs, which resemble IDPs in the reduced state and become globular when their disulfide bonds are formed, illustrate the link between protein folding and aggregation propensities and how these two properties cannot be easily dissociated, determining the main traits of the folding routes followed by these small proteins to attain their native oxidized states. Antioxid. Redox Signal. 21, 368-383.

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Structural Classification of Small, Disulfide-rich Protein Domains

Cited by 89 publications

References 89 publications

Conotoxins: Structure, Therapeutic Potential and Pharmacological Applications

Conotoxins: Structure, Therapeutic Potential and Pharmacological Applications

Conformational characterization of disulfide bonds: A tool for protein classification

Association Between Foldability and Aggregation Propensity in Small Disulfide-Rich Proteins

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