Snake venomics of crotalus tigris: the minimalist toxin arsenal of the deadliest neartic rattlesnake venom: evolutionary clues for generating a pan-specific antivenom against crotalid type II venoms

artículo (arbitrado)-- Universidad de Costa Rica, Instituto de Investigaciones Clodomiro Picado. 2012. This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Proteome Research, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work seehttp://pubs.acs.org/doi/abs/10.1021/pr201021dWe report the proteomic and antivenomic characterization of Crotalus tigris venom. This venom exhibits the highest lethality for mice among rattlesnakes and the simplest toxin proteome reported to date. The venom proteome of C. tigris comprises 7–8 gene products from 6 toxin families: the presynaptic β-neurotoxic heterodimeric PLA2, Mojave toxin, and two serine proteinases comprise, respectively, 66% and 27% of the C. tigris toxin arsenal, whereas a VEGF-like protein, a CRISP molecule, a medium-sized disintegrin, and 1–2 PIII-SVMPs, each represents 0.1–5% of the total venom proteome. This toxin profile really explains the systemic neuro- and myotoxic effects observed in envenomated animals. In addition, we found that venom lethality of C. tigris and other North American rattlesnake type II venoms correlates with the concentration of Mojave toxin A subunit, supporting the view that the neurotoxic venom phenotype of crotalid type II venoms may be described as a single-allele adaptation. Our data suggest that the evolutionary trend towards neurotoxicity, which has been also reported for the South American rattlesnakes, may have resulted by paedomorphism. The ability of an experimental antivenom to effectively immunodeplete proteins from the type II venoms of C. tigris, C. horridus, C. oreganus helleri, C. scutulatus scutulatus, and S. catenatus catenatus, indicated the feasibility of generating a pan-American anti-Crotalus type II antivenom, suggested by the identification of shared evolutionary trends among South American and North American Crotalus.Financed by grants BFU2010-17373 (from the Ministerio de Ciencia e Innovación, Madrid, Spain), CRUSA-CSIC (project 2009CR0021), and PROMETEO/2010/005 from the Generalitat Valenciana (Valencia, Spain), NIH/VIPER resource grant (#5 P40 RR018300-09), and Texas A&M University-Kingsville.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP

Quantitative structure-activity relationship (QSAR) analysis of a series of indole analogues as inhibitor for human group V secretory phospholipase A₂

154-159Phospholipase A₂s (PLA₂) are a class of enzymes, which catalyze the hydrolysis of membrane phospholipids at the sn-2 position to release fatty acids and lysophospholipids. When the fatty acid is arachidonic acid (AA), a complementary metabolism leads to pro-inflammatory mediators collectively known as eicosanoids. Thus, inhibiting PLA₂ activity remains a prime target for the development of new drugs for the treatment of inflammation-related diseases. More than one type of PLA₂s plays a major role in inflammatory disease conditions. In the present study, quantitative structure-activity relationship (QSAR) study was performed for a series of 48 Me-indoxam derivatives as human group V PLA₂ (hVPLA₂) inhibitors, using molecular operating environment (MOE) software. The hVPLA₂ is a secretory PLA2 (sPLA₂), involved in eicosanoid formation in inflammatory cells such as macrophages and mast cells. These studies have come out with three good predictive models (r = 0.82-0.84), which are cross-validated (rcv = 0.68-0.70) by leave-out-one method (Loo). The positive correlation of spatial descriptor Pmiz with inhibitory activity shows that proper orientation of the substitution at R position towards Z-axis is necessary to facilitate the possible interactions of the indole core with active site residues of the PLA₂ enzyme. The negative contribution of b_rotN (atom and bond count-type descriptor) suggests that increasing flexibility conferred by the R substitution is detrimental for the activity. In addition to the hVPLA₂ inhibitory activity is found to be highly influenced by molecular size, energy and polarity of the Me-indoxam derivatives

Crystal and molecular structure of 2,6-bis(4-chlorophenyl)-3-phenylpiperidin-4-one

The crystal structure of the title compound is described. The chemical formula of the compound is C_2_3H_1_9C_l_2NO. The compound is found to crystallize in monoclinic system with space group $P2_1$/c, Z = 4. The unit cell dimensions are a = 15.137(3) $\AA$, b = 8.9171(18) $\AA$, c = 14.779(3) $\AA$, \beta = 91.461(4)° and V = 1994.2(7) $\AA$ 3, Dcalc = 1.320 $gcm^{-3}$. The final R factor is 4.4%. The central piperidone ring of the molecule adopts a slightly distorted chair conformation, the mean torsion angle being 52.3°; the phenyl rings are planar

Identification of a novel family of snake venom proteins veficolins from cerberus rynchops using a venom gland transcriptomics and proteomics approach

10.1021/pr901044xJournal of Proteome Research941882-1893JPRO

Crystal and molecular structure of 2,6-bis(4 fluorobenzylidene)cyclohexanone

The title compound, C_20H_1_6F_2O, crystallizes in triclinic system with P1 space group and the unit cell parameters are: a = 9.700(5), b = 11.834(6), c = 14.315(7) $A^o$, \alpha = 78.464(9), \beta = 74.394(8), \gamma = 86.186(9)°, V = 1551.0(1) $A^o$ 3 and Z = 4. The final R-factor is 4.8%. The cyclohexanone ring adopts a sofa conformation. The different ways of adjusting to steric repulsion results in significant differences between molecule A and B with respect to torsion angles. The steric repulsion between the aromatic groups and hydrogen atoms on the cyclohexanone ring causes increase of the values of bond angles at the C atoms joining the rings and rotation of the corresponding bond, at the expense of conjugation energy of the system. In addition to the van der Waals interactions, C-H...O, C-H...F and C-H...\pi interactions stabilize the molecular packing