Integrin inhibitors from snake venom: Exploring the relationship between the structure and activity of RGD-peptides

Wermelinger, Luciana S.; Geraldo, Reinaldo Barros; Frattani, Flávia Serra; Rodrigues, Carlos Rangel; Juliano, María A.; Castro, Helena C.; Zingali, Russolina B.

doi:10.1016/j.abb.2008.11.023

Cited by 27 publications

(18 citation statements)

References 38 publications

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“…Jarastatin and triflavin are disintegrins that contain six disulfide bonds with the same cysteine pattern, however, these disintegrins have different cystine connectives ( Huang T. F. et al, 1991 ; Coelho et al, 1999 ; Cidade et al, 2006 ). Likewise, triflavin has an elongated and rigid structure composed of turns and antiparallel β-strands, and obtustatin has a compact globular structure composed of turns and without regular secondary structure ( Huang T. F. et al, 1991 ; Coelho et al, 1999 ; Fujii et al, 2003 ; McLane et al, 2004 ; Cidade et al, 2006 ; Wermelinger et al, 2009 ). These cysteine pairing characteristics motivated us to perform a re-analysis of the classification of disintegrins based on the 3D structure to seek a better structural/function comprehension of disintegrins (see point section 4.1).…”

Section: Structural and Evolutive Bases Of Disintegrin Moleculesmentioning

confidence: 99%

Structure-Function Relationship of the Disintegrin Family: Sequence Signature and Integrin Interaction

Vasconcelos

Estrada

David

et al. 2021

Front. Mol. Biosci.

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Disintegrins are small cysteine-rich proteins found in a variety of snake venom. These proteins selectively modulate integrin function, heterodimeric receptors involved in cell-cell and cell-matrix interaction that are widely studied as therapeutic targets. Snake venom disintegrins emerged from the snake venom metalloproteinase and are classified according to the sequence size and number of disulfide bonds. Evolutive structure and function diversification of disintegrin family involves a stepwise decrease in the polypeptide chain, loss of cysteine residues, and selectivity. Since the structure elucidation of echistatin, the description of the structural properties of disintegrins has allowed the investigation of the mechanisms involved in integrin-cell-extracellular matrix interaction. This review provides an analysis of the structures of all family groups enabling the description of an expanded classification of the disintegrin family in seven groups. Each group presents a particular disulfide pattern and sequence signatures, facilitating the identification of new disintegrins. The classification was based on the disintegrin-like domain of the human metalloproteinase (ADAM-10). We also present the sequence and structural signatures important for disintegrin-integrin interaction, unveiling the relationship between the structure and function of these proteins.

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Section: Structural and Evolutive Bases Of Disintegrin Moleculesmentioning

confidence: 99%

Structure-Function Relationship of the Disintegrin Family: Sequence Signature and Integrin Interaction

Vasconcelos

Estrada

David

et al. 2021

Front. Mol. Biosci.

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“…The majority of disintegrins contain the sequence RGD which represents the ancestral integrin-recognition motif [6,22,24,25]. The disulfide bonds around the RGD sequence determine the formation of a loop [20,26e29].…”

Section: Introductionmentioning

confidence: 99%

Isolation and characterization of four medium-size disintegrins from the venoms of Central American viperid snakes of the genera Atropoides, Bothrops, Cerrophidion and Crotalus

Angulo¹,

Castro²,

Lomonte³

et al. 2014

Biochimie

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“…Hopefully it will be expanded to allow investigators to functionally identify new members of the disintegrin family of proteins in blood-sucking arthropods. This database will also provide candidates for understanding structural features of disintegrins [50,74,75,76]. As a final remark, it is somewhat surprising that with exception of Tabanids, none of the Diptera, including mosquitoes, sand flies and biting midges have putative salivary disintegrins, even though three mosquito genomes have been sequenced, indicating that the motif is not at all promiscuous in nature.…”

Section: Discussionmentioning

confidence: 99%

Disintegrins from Hematophagous Sources

Assumpção

Ribeiro

Francischetti

2012

Toxins

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Bloodsucking arthropods are a rich source of salivary molecules (sialogenins) which inhibit platelet aggregation, neutrophil function and angiogenesis. Here we review the literature on salivary disintegrins and their targets. Disintegrins were first discovered in snake venoms, and were instrumental in our understanding of integrin function and also for the development of anti-thrombotic drugs. In hematophagous animals, most disintegrins described so far have been discovered in the salivary gland of ticks and leeches. A limited number have also been found in hookworms and horseflies, and none identified in mosquitoes or sand flies. The vast majority of salivary disintegrins reported display a RGD motif and were described as platelet aggregation inhibitors, and few others as negative modulator of neutrophil or endothelial cell functions. This notably low number of reported disintegrins is certainly an underestimation of the actual complexity of this family of proteins in hematophagous secretions. Therefore an algorithm was created in order to identify the tripeptide motifs RGD, KGD, VGD, MLD, KTS, RTS, WGD, or RED (flanked by cysteines) in sialogenins deposited in GenBank database. The search included sequences from various blood-sucking animals such as ticks (e.g., Ixodes sp., Argas sp., Rhipicephalus sp., Amblyommasp.), tabanids (e.g., Tabanus sp.), bugs (e.g., Triatoma sp., Rhodnius prolixus), mosquitoes (e.g., Anopheles sp., Aedes sp., Culex sp.), sand flies (e.g., Lutzomyia sp., Phlebotomus sp.), leeches (e.g., Macrobdella sp., Placobdella sp.) and worms (e.g., Ancylostoma sp.). This approach allowed the identification of a remarkably high number of novel putative sialogenins with tripeptide motifs typical of disintegrins (>450 sequences) whose biological activity remains to be verified. This database is accessible online as a hyperlinked worksheet and displays biochemical, taxonomic, and gene ontology aspects for each putative disintegrin. It is also freely available for download (right click with the mouse) at links (web version) and (stand alone version).

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Integrin inhibitors from snake venom: Exploring the relationship between the structure and activity of RGD-peptides

Cited by 27 publications

References 38 publications

Structure-Function Relationship of the Disintegrin Family: Sequence Signature and Integrin Interaction

Structure-Function Relationship of the Disintegrin Family: Sequence Signature and Integrin Interaction

Isolation and characterization of four medium-size disintegrins from the venoms of Central American viperid snakes of the genera Atropoides, Bothrops, Cerrophidion and Crotalus

Disintegrins from Hematophagous Sources

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