Primary structures of four trypsin inhibitor E homologs from venom of Dendroaspis angusticeps: structure–function comparisons with other dendrotoxin homologs

Sigle, Randy O.; Hackett, Murray; Aird, Steven D.

doi:10.1016/s0041-0101(01)00227-6

Cited by 5 publications

(5 citation statements)

References 54 publications

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“…Kunitz serine protease inhibitors have been recognized for decades as a family of short, structurally similar toxins (59–61 residues with three disulfides) with diverse functions ranging from non-neurotoxic inhibitors of trypsin or chymotrypsin to neurotoxic ligands of potassium and calcium channels, such as the dendrotoxins [74,127,128,129,130,131]. Dufton [132] noted that relatively few amino acid substitutions are necessary to turn a protease inhibitor into a dendrotoxin.…”

Section: Resultsmentioning

confidence: 99%

Coralsnake Venomics: Analyses of Venom Gland Transcriptomes and Proteomes of Six Brazilian Taxa

Aird

Silva

Qiu

et al. 2017

Toxins

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Venom gland transcriptomes and proteomes of six Micrurus taxa (M. corallinus, M. lemniscatus carvalhoi, M. lemniscatus lemniscatus, M. paraensis, M. spixii spixii, and M. surinamensis) were investigated, providing the most comprehensive, quantitative data on Micrurus venom composition to date, and more than tripling the number of Micrurus venom protein sequences previously available. The six venomes differ dramatically. All are dominated by 2–6 toxin classes that account for 91–99% of the toxin transcripts. The M. s. spixii venome is compositionally the simplest. In it, three-finger toxins (3FTxs) and phospholipases A2 (PLA2s) comprise >99% of the toxin transcripts, which include only four additional toxin families at levels ≥0.1%. Micrurus l. lemniscatus venom is the most complex, with at least 17 toxin families. However, in each venome, multiple structural subclasses of 3FTXs and PLA2s are present. These almost certainly differ in pharmacology as well. All venoms also contain phospholipase B and vascular endothelial growth factors. Minor components (0.1–2.0%) are found in all venoms except that of M. s. spixii. Other toxin families are present in all six venoms at trace levels (<0.005%). Minor and trace venom components differ in each venom. Numerous novel toxin chemistries include 3FTxs with previously unknown 8- and 10-cysteine arrangements, resulting in new 3D structures and target specificities. 9-cysteine toxins raise the possibility of covalent, homodimeric 3FTxs or heterodimeric toxins with unknown pharmacologies. Probable muscarinic sequences may be reptile-specific homologs that promote hypotension via vascular mAChRs. The first complete sequences are presented for 3FTxs putatively responsible for liberating glutamate from rat brain synaptosomes. Micrurus C-type lectin-like proteins may have 6–9 cysteine residues and may be monomers, or homo- or heterodimers of unknown pharmacology. Novel KSPIs, 3× longer than any seen previously, appear to have arisen in three species by gene duplication and fusion. Four species have transcripts homologous to the nociceptive toxin, (MitTx) α-subunit, but all six species had homologs to the β-subunit. The first non-neurotoxic, non-catalytic elapid phospholipase A2s are reported. All are probably myonecrotic. Phylogenetic analysis indicates that the six taxa diverged 15–35 million years ago and that they split from their last common ancestor with Old World elapines nearly 55 million years ago. Given their early diversification, many cryptic micrurine taxa are anticipated.

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Section: Resultsmentioning

confidence: 99%

Coralsnake Venomics: Analyses of Venom Gland Transcriptomes and Proteomes of Six Brazilian Taxa

Aird

Silva

Qiu

et al. 2017

Toxins

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“…DtxB and DtxE from D. polylepis polylepis and their homologs from Dendroaspis angusticeps (ϵ‐Dtxs) show strong protease inhibitory activity and weak K + channel inhibition [41–43]. The separate position of DtxB from the Dtx group indicates that the neurotoxic lineage evolved after gene duplication.…”

Section: Resultsmentioning

confidence: 99%

“…The separate position of DtxB from the Dtx group indicates that the neurotoxic lineage evolved after gene duplication. On the basis of the biological activity and structural differences it has been proposed that ϵ‐Dtxs have structural and functional characteristics that are intermediate between protease inhibitors and their neurotoxic homologs [43]. Calcicludine, which is a Ca + channel blocker in D. angusticeps , evolved after gene duplication and functional diversification.…”

Section: Resultsmentioning

confidence: 99%

Adaptive evolution in the snake venom Kunitz/BPTI protein family

2003

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Snake venoms are rich sources of serine proteinase inhibitors that are members of the Kunitz/BPTI (bovine pancreatic trypsin inhibitor) family. However, only a few of their gene sequences have been determined from snakes. We therefore cloned the cDNAs for the trypsin and chymotrypsin inhibitors from a Vipera ammodytes venom gland cDNA library. Phylogenetic analysis of these and other snake Kunitz/BPTI homologs shows the presence of three clusters, where sequences cluster by functional role. Analysis of the nucleotide sequences from the snake Kunitz/BPTI family shows that positive Darwinian selection was operating on the highly conserved BPTI fold, indicating that this family evolved by gene duplication and rapid diversi¢cation.

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“…The dendrotoxins are related to a group of proteins called the Kunitz serine protease inhibitors; in fact, some dendrotoxins still retain weak trypsin inhibitory activity [Harvey, 2001;Sigle et al, 2001]. Peptides with K + channel blocking properties have also been isolated from sea anemones [Schweitz et al, 1995].…”

Section: Convergent Evolution Of Neurotoxinsmentioning

confidence: 99%

Convergent Evolution on the Molecular Level

Zakon¹

2002

Brain Behav Evol

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Divergence and convergence are two evolutionary processes by which organisms become adapted to their environments. With the advent of molecular biological techniques it is possible to ask if these processes are observed at the molecular level. There are many examples of molecular divergence in which molecular sequence or function change over evolutionary time. There are fewer reports of convergent evolution on the molecular level, and these claims are sometimes controversial. In this paper I discuss the types of convergent molecular evolution, describe the criteria for accepting or rejecting convergence, and give some examples relevant to neurobiology where convergence has been claimed. These include convergent evolution of opsins, gap junction proteins, neurotransmitter receptors, ion channels, and venoms directed against ion channels.

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Primary structures of four trypsin inhibitor E homologs from venom of Dendroaspis angusticeps: structure–function comparisons with other dendrotoxin homologs

Cited by 5 publications

References 54 publications

Coralsnake Venomics: Analyses of Venom Gland Transcriptomes and Proteomes of Six Brazilian Taxa

Coralsnake Venomics: Analyses of Venom Gland Transcriptomes and Proteomes of Six Brazilian Taxa

Adaptive evolution in the snake venom Kunitz/BPTI protein family

Convergent Evolution on the Molecular Level

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