 | This is the sandbox page where you will draft your initial Wikipedia contribution.
If you're starting a new article, you can develop it here until it's ready to go live. If you're working on improvements to an existing article, copy only one section at a time of the article to this sandbox to work on, and be sure to use an edit summary linking to the article you copied from. Do not copy over the entire article. You can find additional instructions here. Remember to save your work regularly using the "Publish page" button. (It just means 'save'; it will still be in the sandbox.) You can add bold formatting to your additions to differentiate them from existing content. |
Article Draft
editAtrolysin A (EC 3.4.24.1, Crotalus atrox metalloendopeptidase a, hemorrhagic toxin a, Crotalus atrox alpha-proteinase, Crotalus atrox proteinase, bothropasin) is an enzyme.[1][2][3][4] This enzyme catalyses the following chemical reaction
- Cleavage of Asn3-Gln4, His5-Leu6, His10-Leu11, Ala14-Leu15 and Tyr16-Leu17 in insulin B chain; removes C-terminal Leu from small peptides
This endopeptidase is one of six hemorrhagic toxins in the venom of western diamondback rattlesnake.
Atrolysin A contains a metalloproteinase disintegrin-like domain as well as a cysteine-rich domain.[5] The metalloproteinase disintegrin-like domain has shown an ability to degrade sub-endothelial matrix proteins such as type IV collagen, and fibronectin[6] which is partially responsible for the hemorrhage caused by the toxin. The cysteine-rich domain binds to the alpha-2/beta-1 integrin and causes inhibition of the platelet aggregation pathways that collagen is responsible for.[7][6]The glycoprotein VI (GPVI) collagen receptor however, does not seem affected by atrolysin A or other snake venom metalloproteinases (SVMP ).[8] Other agonists for platelet formation and aggregation such as adenosine diphosphate (ADP) or pathways mediated by convulxin also do not seem inhibited by the toxin in most organisms.[6][9][10]
Research further suggests that in some cases, this enzyme has the potential to inhibit platelet formation with certain pathways that were previously determined that the toxin had no effect on. For example, ADP stimulated aggregation appears to be inhibited by atrolysin A in a study where insect cells were used to express the protein, and the protein was inserted into human blood. When this variant of the protein was inserted into human blood, ADP stimulated platelet aggregation was inhibited[5]. This form of platelet aggregation does not appear inhibited by atrolysin A in other studies. This suggests that there may be an interaction between the disintegrin-like domain, and cysteine-rich domain of atrolysin A and fibrinogen receptor alpha-2b/beta-3 as well as the collagen receptor.[5]
The cysteine-rich domain was shown to have two sequences that cause an interaction which prevents alpha-2/beta-1 integrin expressing K562 cells and platelets from binding to collagen[8].
Amino Acid Sequence and Protein Structure
editThe amino acid sequence of atrolysin A is 419 sequences long, and contains ten amino acid positions calcium binding sites between positions 9 and 225, some of these calcium binding sites require carbonyl oxygen[6]. There are also three positions (142, 146, 152) that are used for binding with the enzyme's cofactor, zinc. The active site lies at position 143.[6]
A significant portion of the protein from position 1-190 consists of alpha-helical structures with two shorted helixes between positions 315-340.[11]There are 39 observed disulfide bonds in the protein, all but one of these disulfide bonds occur between positions 157-409. Research suggests that the RSECD cysteine residue at positions 272-276 must be involved in a disulfide bond for the enzyme to have an inhibitory affect on platelet aggregation.[6] [5]
Isozymes
editOther atrolysin isozymes (A-F) have been further studied to understand potential methods of treatment against SVMPs. Research has been conducted on the use of medications to treat other diseases such as arthritis, and tumor metastasis as well.[12]
References
edit- ^ Bjarnason JB, Tu AT (August 1978). "Hemorrhagic toxins from Western diamondback rattlesnake (Crotalus atrox) venom: isolation and characterization of five toxins and the role of zinc in hemorrhagic toxin e". Biochemistry. 17 (16): 3395–404. doi:10.1021/bi00609a033. PMID 210790.
- ^ Mori N, Nikai T, Sugihara H, Tu AT (February 1987). "Biochemical characterization of hemorrhagic toxins with fibrinogenase activity isolated from Crotalus ruber ruber venom". Archives of Biochemistry and Biophysics. 253 (1): 108–21. doi:10.1016/0003-9861(87)90643-6. PMID 2949699.
- ^ Bjarnason JB, Hamilton D, Fox JW (May 1988). "Studies on the mechanism of hemorrhage production by five proteolytic hemorrhagic toxins from Crotalus atrox venom". Biological Chemistry Hoppe-Seyler. 369 Suppl: 121–9. PMID 3060135.
- ^ Bjarnason JB, Fox JW (1989). "Hemorrhagic toxins from snake venoms". Journal of Toxicology: Toxin Reviews. 7 (2): 121–209. doi:10.3109/15569548809059729.
- ^ a b c d Jia, Li-Guo; Wang, Xiao-Ming; Shannon, John D.; Bjarnason, Jon B.; Fox, Jay W. (1997). "Function of Disintegrin-like/Cysteine-rich Domains of Atrolysin A". Journal of Biological Chemistry. 272 (20): 13094–13102. doi:10.1074/jbc.272.20.13094.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ a b c d e f "Zinc metalloproteinase-disintegrin-like atrolysin-A - Crotalus atrox (Western diamondback rattlesnake)". www.uniprot.org. Retrieved 2021-10-29.
- ^ Serrano, Solange M. T.; Jia, Li-Guo; Wang, Deyu; Shannon, John D.; Fox, Jay W. (2005-10-01). "Function of the cysteine-rich domain of the haemorrhagic metalloproteinase atrolysin A: targeting adhesion proteins collagen I and von Willebrand factor". Biochemical Journal. 391 (1): 69–76. doi:10.1042/BJ20050483. ISSN 0264-6021. PMC 1237140. PMID 15929722.
{{cite journal}}: no-break space character in|first4=at position 5 (help); no-break space character in|first5=at position 4 (help); no-break space character in|first=at position 8 (help)CS1 maint: PMC format (link) - ^ a b Kamiguti, Aura S.; Gallagher, Paul; Marcinkiewicz, Cezary; Theakston, R.David G.; Zuzel, Mirko; Fox, Jay W. (2003-08-14). "Identification of sites in the cysteine-rich domain of the class P-III snake venom metalloproteinases responsible for inhibition of platelet function". FEBS Letters. 549 (1–3): 129–134. doi:10.1016/S0014-5793(03)00799-3.
- ^ Puri, R. N.; Colman, R. W. (1997). "ADP-induced platelet activation". Critical Reviews in Biochemistry and Molecular Biology. 32 (6): 437–502. doi:10.3109/10409239709082000. ISSN 1040-9238. PMID 9444477.
- ^ Francischetti, I. M.; Ghazaleh, F. A.; Reis, R. A.; Carlini, C. R.; Guimarães, J. A. (1998-05-15). "Convulxin induces platelet activation by a tyrosine-kinase-dependent pathway and stimulates tyrosine phosphorylation of platelet proteins, including PLC gamma 2, independently of integrin alpha IIb beta 3". Archives of Biochemistry and Biophysics. 353 (2): 239–250. doi:10.1006/abbi.1998.0598. ISSN 0003-9861. PMID 9606958.
- ^ "Q92043 | SWISS-MODEL Repository". swissmodel.expasy.org. Retrieved 2021-10-29.
- ^ Zhang, D; Botos, I; Gomis-Rüth, F X; Doll, R; Blood, C; Njoroge, F G; Fox, J W; Bode, W; Meyer, E F (1994-08-30). "Structural interaction of natural and synthetic inhibitors with the venom metalloproteinase, atrolysin C (form d)". Proceedings of the National Academy of Sciences of the United States of America. 91 (18): 8447–8451. ISSN 0027-8424. PMID 8078901.