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Venomics of Calloselasma rhodostoma, the Malayan pit viper: A complex toxin arsenal unraveled.
J Proteomics. 2016 10 04; 148:44-56.JP

Abstract

The venom of Malayan pit viper (Calloselasma rhodostoma) is highly toxic but also valuable in drug discovery. However, a comprehensive proteome of the venom that details its toxin composition and abundance is lacking. This study aimed to unravel the venom complexity through a multi-step venomic approach. At least 96 distinct proteins (29 basic, 67 acidic) in 11 families were identified from the venom. The venom consists of mainly snake venom metalloproteinases (SVMP, 41.17% of total venom proteins), within which the P-I (kistomin, 20.4%) and P-II (rhodostoxin, 19.8%) classes predominate. This is followed by C-type lectins (snaclec, 26.3%), snake venom serine protease (SVSP, 14.9%), L-amino acid oxidase (7.0%), phospholipase A2 (4.4%), cysteine-rich secretory protein (2.5%), and five minor toxins (nerve growth factor, neurotrophin, phospholipase B, 5' nucleotidase and phosphodiesterase, totaling 2.6%) not reported in the proteome hitherto. Importantly, all principal hemotoxins unveiled correlate with the syndrome: SVSP ancrod causes venom-induced consumptive coagulopathy, aggravated by thrombocytopenia caused by snaclec rhodocytin, a platelet aggregation inducer, while P-II rhodostoxin mediates hemorrhage, exacerbated by P-I kistomin and snaclec rhodocetin that inhibit platelet plug formation. These toxins exist in multiple isoforms and/or complex subunits, deserving further characterization for the development of an effective, polyspecific regional antivenom.

BIOLOGICAL SIGNIFICANCE

Advents in proteomics and bioinformatics have vigorously propelled the scientific discoveries of toxins from various lineages of venomous snakes. The Malayan pit viper, Calloselasma rhodostoma, is a medically important species in Southeast Asia as its bite can cause envenomation, while the venom is also a source of bioactive compounds for drug discovery. Detailed profiling of the venom, however, is inadequate possibly due to the complex nature of the venom and technical limitation in separating the constituents into details. Integrating a multi-step fractionation method, this study successfully revealed a comprehensive and quantitative profile of the composition of the venom of this medically important venomous snake. The relative abundance of the various venom proteins is determined in a global profile, providing useful information for understanding the pathogenic roles of the different toxins in C. rhodostoma envenomation. Notably, the principal hemotoxins were identified in great details, including the variety of toxin subunits and isoforms. The findings indicate that these toxins are the principal targets for effective antivenom neutralization, and should be addressed in the production of a pan-regional polyspecific antivenom. In addition, minor toxin components not reported previously in the venom were also detected in this study, enriching the current toxin database for the venomous snakes.

Authors+Show Affiliations

Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. Electronic address: tanchoohock@gmail.com.Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. Electronic address: tanngethong@yahoo.com.sg.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27418434

Citation

Tang, Esther Lai Har, et al. "Venomics of Calloselasma Rhodostoma, the Malayan Pit Viper: a Complex Toxin Arsenal Unraveled." Journal of Proteomics, vol. 148, 2016, pp. 44-56.
Tang EL, Tan CH, Fung SY, et al. Venomics of Calloselasma rhodostoma, the Malayan pit viper: A complex toxin arsenal unraveled. J Proteomics. 2016;148:44-56.
Tang, E. L., Tan, C. H., Fung, S. Y., & Tan, N. H. (2016). Venomics of Calloselasma rhodostoma, the Malayan pit viper: A complex toxin arsenal unraveled. Journal of Proteomics, 148, 44-56. https://doi.org/10.1016/j.jprot.2016.07.006
Tang EL, et al. Venomics of Calloselasma Rhodostoma, the Malayan Pit Viper: a Complex Toxin Arsenal Unraveled. J Proteomics. 2016 10 4;148:44-56. PubMed PMID: 27418434.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Venomics of Calloselasma rhodostoma, the Malayan pit viper: A complex toxin arsenal unraveled. AU - Tang,Esther Lai Har, AU - Tan,Choo Hock, AU - Fung,Shin Yee, AU - Tan,Nget Hong, Y1 - 2016/07/11/ PY - 2016/04/26/received PY - 2016/06/26/revised PY - 2016/07/07/accepted PY - 2016/7/16/entrez PY - 2016/7/16/pubmed PY - 2017/11/29/medline KW - Calloselasma rhodostoma KW - Coagulopathy KW - LC-MS/MS KW - Malayan pit viper KW - Venom proteome KW - Venomics SP - 44 EP - 56 JF - Journal of proteomics JO - J Proteomics VL - 148 N2 - UNLABELLED: The venom of Malayan pit viper (Calloselasma rhodostoma) is highly toxic but also valuable in drug discovery. However, a comprehensive proteome of the venom that details its toxin composition and abundance is lacking. This study aimed to unravel the venom complexity through a multi-step venomic approach. At least 96 distinct proteins (29 basic, 67 acidic) in 11 families were identified from the venom. The venom consists of mainly snake venom metalloproteinases (SVMP, 41.17% of total venom proteins), within which the P-I (kistomin, 20.4%) and P-II (rhodostoxin, 19.8%) classes predominate. This is followed by C-type lectins (snaclec, 26.3%), snake venom serine protease (SVSP, 14.9%), L-amino acid oxidase (7.0%), phospholipase A2 (4.4%), cysteine-rich secretory protein (2.5%), and five minor toxins (nerve growth factor, neurotrophin, phospholipase B, 5' nucleotidase and phosphodiesterase, totaling 2.6%) not reported in the proteome hitherto. Importantly, all principal hemotoxins unveiled correlate with the syndrome: SVSP ancrod causes venom-induced consumptive coagulopathy, aggravated by thrombocytopenia caused by snaclec rhodocytin, a platelet aggregation inducer, while P-II rhodostoxin mediates hemorrhage, exacerbated by P-I kistomin and snaclec rhodocetin that inhibit platelet plug formation. These toxins exist in multiple isoforms and/or complex subunits, deserving further characterization for the development of an effective, polyspecific regional antivenom. BIOLOGICAL SIGNIFICANCE: Advents in proteomics and bioinformatics have vigorously propelled the scientific discoveries of toxins from various lineages of venomous snakes. The Malayan pit viper, Calloselasma rhodostoma, is a medically important species in Southeast Asia as its bite can cause envenomation, while the venom is also a source of bioactive compounds for drug discovery. Detailed profiling of the venom, however, is inadequate possibly due to the complex nature of the venom and technical limitation in separating the constituents into details. Integrating a multi-step fractionation method, this study successfully revealed a comprehensive and quantitative profile of the composition of the venom of this medically important venomous snake. The relative abundance of the various venom proteins is determined in a global profile, providing useful information for understanding the pathogenic roles of the different toxins in C. rhodostoma envenomation. Notably, the principal hemotoxins were identified in great details, including the variety of toxin subunits and isoforms. The findings indicate that these toxins are the principal targets for effective antivenom neutralization, and should be addressed in the production of a pan-regional polyspecific antivenom. In addition, minor toxin components not reported previously in the venom were also detected in this study, enriching the current toxin database for the venomous snakes. SN - 1876-7737 UR - https://www.unboundmedicine.com/medline/citation/27418434/Venomics_of_Calloselasma_rhodostoma_the_Malayan_pit_viper:_A_complex_toxin_arsenal_unraveled_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1874-3919(16)30302-5 DB - PRIME DP - Unbound Medicine ER -