Disintegrin

Disintegrin
Structure of disintegrin heterodimer from Echis carinatus
Identifiers
SymbolDisintegrin
PfamPF00200
InterProIPR001762
PROSITEPDOC00351
SCOP21kst / SCOPe / SUPFAM
OPM superfamily227
OPM protein2ao7
Membranome538
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

Disintegrins are a family of small proteins (45–84 amino acids in length) from viper venoms that function as potent inhibitors of both platelet aggregation and integrin-dependent cell adhesion.[1][2][3]

Operation

Disintegrins work by countering the blood clotting steps, inhibiting the clumping of platelets. They interact with the beta-1 and -3 families of integrins receptors. Integrins are cell receptors involved in cell–cell and cell–extracellular matrix interactions, serving as the final common pathway leading to aggregation via formation of platelet–platelet bridges, which are essential in thrombosis and haemostasis. Disintegrins contain an RGD (Arg-Gly-Asp) or KGD (Lys-Gly-Asp) sequence motif that binds specifically to integrin IIb-IIIa receptors on the platelet surface, thereby blocking the binding of fibrinogen to the receptor–glycoprotein complex of activated platelets. Disintegrins act as receptor antagonists, inhibiting aggregation induced by ADP, thrombin, platelet-activating factor and collagen.[4] The role of disintegrin in preventing blood coagulation renders it of medical interest, particularly with regard to its use as an anti-coagulant.[5]

Types of disintegrin

Disintegrins from different snake species have been characterised: albolabrin, applagin, barbourin, batroxostatin, bitistatin, obtustatin,[6] schistatin,[7] echistatin,[8] elegantin, eristicophin, flavoridin,[9] halysin, kistrin, mojastin (Crotalus scutulatus), rubistatin (Crotalus ruber), tergeminin, salmosin,[10] tzabcanin (Crotalus simus tzabcan)[11] and triflavin.

Disintegrins are split into 5 classes: small, medium, large, dimeric, and snake venom metalloproteinases.[12]

Small Disintegrins: 49-51 amino acids, 4 disulfide bonds
Medium Disintegrins: 70 amino acids, 6 disulfide bonds
Large Disintegrins: 84 amino acids, 7 disulfide bonds
Dimeric Disintegrins: 67 amino acids, 4 intra-chain disulfide bonds
Snake Venom Metalloproteinases: 100 amino acids, 8 disulfide bond

Evolution of disintegrin family

Disintegrins evolved via gene duplication of an ancestral protein family, the ADAM family. Small, medium, large, and dimeric disintegrin family are found only in the family Viperidae, suggesting duplication and diversification about 12-20 million years ago. Snake venom metalloproteinases are found through the entire superfamily Colubroidea, suggesting that they evolved before Colubroidea diversified roughly 60 million years ago.[13]

Other sources of disintegrin proteins

Disintegrin-like proteins are found in various species ranging from slime mold to humans. Some other proteins known to contain a disintegrin domain are:

  • Some snake venom zinc metalloproteinases[14] consist of an N-terminal catalytic domain fused to a disintegrin domain. Such is the case for trimerelysin I (HR1B), atrolysin E (Ht-e) and trigramin. It has been suggested that these proteinases are able to cleave themselves from the disintegrin domains and that the latter may arise from such a post-translational processing.
  • ADAM and ADAMTS protein families, which include important protease enzymes.
    • The secreted protease ADAMTS13, found in serum, cleaves Von Willebrand factor and acts as a natural, endogenous inhibitor of platelet adhesion and aggregation.
    • ADAM2 (beta-fertilin, the beta-subunit of guinea pig sperm surface protein PH30).[15] PH30 is a protein involved in sperm-egg fusion. The beta subunit contains a disintegrin at the N-terminal extremity.
    • ADAM7 (Mammalian epididymial apical protein 1, EAP I).[16] ADAM7 is associated with the sperm membrane and may play a role in sperm maturation. Structurally, ADAM7 consists of an N-terminal domain, followed by a zinc metalloproteinase domain, a disintegrin domain, and a large C-terminal domain that contains a transmembrane region.

See also

References

  1. ^ Oliveira, Ana L.; Viegas, Matilde F.; da Silva, Saulo L.; Soares, Andreimar M.; Ramos, Maria J.; Fernandes, Pedro A. (July 2022). "The chemistry of snake venom and its medicinal potential". Nature Reviews Chemistry. 6 (7): 451–469. doi:10.1038/s41570-022-00393-7. ISSN 2397-3358. PMC 9185726.
  2. ^ McLane MA, Sanchez EE, Wong A, Paquette-Straub C, Perez JC (2004). "Disintegrins". Curr Drug Targets Cardiovasc Haematol Disord. 4 (4): 327–55. doi:10.2174/1568006043335880. PMID 15578957.
  3. ^ Lu X, Lu D, Scully MF, Kakkar VV (2005). "Snake venom metalloproteinase containing a disintegrin-like domain, its structure-activity relationships at interacting with integrins". Curr Med Chem Cardiovasc Hematol Agents. 3 (3): 249–60. doi:10.2174/1568016054368205. PMID 15974889.
  4. ^ Rahman S, Xu CS (2001). "Identification by Site-directed Mutagenesis of Amino Acid Residues Flanking RGD Motifs of Snake Venom Disintegrins for Their Structure and Function". Acta Biochim. Biophys. Sin. 33 (2): 153–157. PMID 12050803.
  5. ^ Lu X, Lu D, Scully MF, Kakkar VV (2006). "Integrins in drug targeting-RGD templates in toxins". Curr Pharm Des. 12 (22): 2749–69. doi:10.2174/138161206777947713. PMID 16918409.
  6. ^ Calvete JJ, Monleon D, Celda B, Paz Moreno-Murciano M, Marcinkiewicz C (2003). "NMR solution structure of the non-RGD disintegrin obtustatin". J. Mol. Biol. 329 (1): 135–45. doi:10.1016/S0022-2836(03)00371-1. PMID 12742023.
  7. ^ Betzel C, Sharma S, Singh TP, Perbandt M, Yadav S, Kaur P, Bilgrami S (2005). "Crystal structure of the disintegrin heterodimer from saw-scaled viper (Echis carinatus) at 1.9 A resolution". Biochemistry. 44 (33): 11058–66. doi:10.1021/bi050849y. PMID 16101289.
  8. ^ Calvete JJ, Kovacs H, Monleon D, Celda B, Esteve V (2005). "Conformation and concerted dynamics of the integrin-binding site and the C-terminal region of echistatin revealed by homonuclear NMR". Biochem J. 387 (Pt 1): 57–66. doi:10.1042/BJ20041343. PMC 1134932. PMID 15535803.
  9. ^ Mizuno H, Morita T, Fujii Y, Fujimoto Z, Horii K, Okuda D (2003). "Crystal structure of trimestatin, a disintegrin containing a cell adhesion recognition motif RGD". J. Mol. Biol. 332 (5): 1115–22. doi:10.1016/S0022-2836(03)00991-4. PMID 14499613.
  10. ^ Lee W, Shin J, Kang I, Hong SY, Chung K, Jang Y, Kim DS (2003). "Solution structure of a novel disintegrin, salmosin, from Agkistrondon halys venom". Biochemistry. 42 (49): 14408–15. doi:10.1021/bi0300276. PMID 14661951.
  11. ^ Saviola, A.J., Modahl, C.M. and Mackessy, S.P., 2015. Disintegrins of Crotalus simus tzabcan venom: Isolation, characterization and evaluation of the cytotoxic and anti-adhesion activities of tzabcanin, a new RGD disintegrin. Biochimie, 116, pp.92-102. https://doi.org/10.1016/j.biochi.2015.07.005
  12. ^ Calvete, J (2005). "Structure-function correlations of snake venom disintegrins". Curr Pharm Des. 11 (7): 825–835. doi:10.2174/1381612053381783. PMID 15777237.
  13. ^ Juárez P, Comas I, González-Candelas F, Calvete JJ (2008). "Evolution of Snake Venom Disintegrins by Positive Darwinian Selection". Molecular Biology and Evolution. 25 (11): 2391–2407. doi:10.1093/molbev/msn179. PMID 18701431.
  14. ^ Teixeira Cde F, Fernandes CM, Zuliani JP, Zamuner SF (2005). "Inflammatory effects of snake venom metalloproteinases". Mem. Inst. Oswaldo Cruz. 100: 181–4. doi:10.1590/s0074-02762005000900031. hdl:1807/8219. PMID 15962120.
  15. ^ Turck CW, Myles DG, Primakoff P, Blobel CP, Wolfsberg TG, White JM (1992). "A potential fusion peptide and an integrin ligand domain in a protein active in sperm-egg fusion". Nature. 356 (6366): 248–252. Bibcode:1992Natur.356..248B. doi:10.1038/356248a0. PMID 1552944. S2CID 4233338.
  16. ^ Hall L, Jones R, Barker PJ, Perry AC (1992). "A mammalian epididymal protein with remarkable sequence similarity to snake venom haemorrhagic peptides". Biochem. J. 286 (3): 671–675. doi:10.1042/bj2860671. PMC 1132955. PMID 1417724.
This article incorporates text from the public domain Pfam and InterPro: IPR001762

Read other articles:

Yayat T. Soemitra

Yayat Turochmat Soemitra Pelaksana Tugas Bupati Bandung BaratMasa jabatan19 April 2018 – 19 Juli 2018PresidenJoko WidodoGubernurAhmad HeryawanMochammad Iriawan (pj.) PendahuluAbu BakarPenggantiDadang Mohammad Masoem (pj.)Aa Umbara SutisnaWakil Bupati Bandung Barat ke-2Masa jabatan17 Juli 2013 – 19 April 2018PresidenSusilo Bambang YudhoyonoJoko WidodoGubernurAhmad HeryawanBupatiAbu Bakar PendahuluErnawan NatasaputraPenggantiHengky Kurniawan Informasi pribadiLahirYayat...

 

 

Gua es

Gua es Dachstein-Rieseneishöhle di Austria Gua es adalah semua jenis gua alam (sering kali berupa tabung lava atau gua batu kapur) yang mengandung sejumlah besar es abadi (es yang menyelimuti sepanjang tahun). Untuk dapat diklasifikasikan sebagai gua es, setidaknya sebagian dari gua harus memiliki suhu di bawah 0 °C (32 °F) sepanjang tahun, dan air harus mengalir ke zona dingin gua. Bacaan lanjutan Macdonald, W.D. Mechanisms for Ice Development in Ice Caves of Western North Ameri...

 

 

List of acts of the Parliament of the United Kingdom from 1977

Part of a series onBritish law Acts of Parliament of the United Kingdom Year      1801 1802 1803 1804 1805 1806 1807 1808 1809 1810 1811 1812 1813 1814 1815 1816 1817 1818 1819 1820 1821 1822 1823 1824 1825 1826 1827 1828 1829 1830 1831 1832 1833 1834 1835 1836 1837 1838 1839 1840 1841 1842 1843 1844 1845 1846 1847 1848 1849 1850 1851 1852 1853 1854 1855 1856 1857 1858 1859 1860 1861 1862 1863 1864 1865 1866 1867 1868 1869 1870 1871 1872 1873 1874 1875 1876 1877 1878 ...

Alaska Peninsula

Peninsula extending towards the Aleutian Islands in Southwest Alaska, United States This article is about a region in Southwest Alaska. For the entire state, see Alaska. Map of Alaska Peninsula Volcanoes on the Alaska Peninsula Peulik Volcano and cottongrass meadow The Alaska Peninsula[1] (also called Aleut Peninsula[2] or Aleutian Peninsula,[3] Aleut: Alasxix̂; Sugpiaq: Aluuwiq, Al'uwiq) is a peninsula extending about 497 mi (800 km) to the southwest from t...

 

 

Ls

Command to list files and directories in Unix and Unix-like operating systems For other uses, see LS. lsLong file listing with ls --color=auto -l in Linux showing various modes, date formats, colors and appended indicators (executables and directories).Original author(s)coreutils: Richard Stallman and David MacKenzieDeveloper(s)Various open-source and commercial developersWritten inCOperating systemMultics, Unix, Unix-like, Plan 9, Inferno, MSX-DOSTypeCommandLicensecoreutils: GPLv3+BusyBox: G...

 

 

Rapovce

Roman Catholic church in Rapovce Location of Lučenec District in the Banská Bystrica Region Rapovce (Hungarian: Rapp) is a village and municipality in the Lučenec District in the Banská Bystrica Region of Slovakia. External links http://www.statistics.sk/mosmis/eng/run.html Wikimedia Commons has media related to Rapovce. vteMunicipalities of Lučenec District Lučenec Fiľakovo Ábelová Belina Biskupice Boľkovce Budiná Bulhary Buzitka Čakanovce Čamovce Divín Dobroč Fiľakovské Kov...

Nicho Bears and Bar

Gay bar in Mexico City, Mexico Nicho Bears and BarInterior bar, 2018AddressLondres 182, Juárez, CuauhtémocMexico CityMexicoCoordinates19°25′27″N 99°09′58″W / 19.42423673228874°N 99.16615950635277°W / 19.42423673228874; -99.16615950635277 Nicho Bears and Bar is a gay bar in Zona Rosa, Mexico City, Mexico.[1] Passport Magazine's Joseph Pedro said the bar offers low-key bear night[s] where you're assigned numbers for secret messages.[2] I...

 

 

Prime Minister of Thailand

Head of government of Thailand For a list of head of government, see List of prime ministers of Thailand. Prime Minister of the Kingdom of Thailandนายกรัฐมนตรีแห่งราชอาณาจักรไทยPrime Ministerial SealPrime Ministerial StandardIncumbentSrettha Thavisinsince 22 August 2023[1]Office of the Prime MinisterRoyal Thai GovernmentStyleHis ExcellencyStatusHead of governmentMember ofRoyal Thai CabinetNational Security CouncilInterna...

 

 

Andrii Sybiha

Ukrainian politicianThis article may have been created or edited in return for undisclosed payments, a violation of Wikipedia's terms of use. It may require cleanup to comply with Wikipedia's content policies, particularly neutral point of view. (January 2024)Andrii SybihaАндрій СибігаSybiha in 2022Deputy Head of the Office of the President of UkraineIncumbentAssumed office May 31, 2021PresidentVolodymyr Zelenskyy Personal detailsBorn (1975-01-01) 1 January 1975 (age 49)Z...

Communist Party of Turkmenistan

Ruling party of the Turkmen SSR (1924–1991) For the party founded in 1998, see Communist Party of Turkmenistan (1998). You can help expand this article with text translated from the corresponding article in Russian. (February 2013) Click [show] for important translation instructions. View a machine-translated version of the Russian article. Machine translation, like DeepL or Google Translate, is a useful starting point for translations, but translators must revise errors as necessary a...

 

 

Padma Sundar Malla

Artikel ini sebatang kara, artinya tidak ada artikel lain yang memiliki pranala balik ke halaman ini.Bantulah menambah pranala ke artikel ini dari artikel yang berhubungan atau coba peralatan pencari pranala.Tag ini diberikan pada Januari 2023. Padma Sundar Malla pada 1950an Padma Sundar Malla (1890–1974) (bahasa Nepali: पद्मसुन्दर मल्ल) adalah insinyur kelistrikan pertama di Nepal dan tokoh Nepal pertama yang mengunjungi Amerika Serikat. Ia mempelopori gener...

 

 

Visby

Panorama kota Visby Visby merupakan nama kota di Swedia yang terletak di Pulau Gotland. Penduduknya berjumlah 22.017 jiwa. Visby adalah ibu kota provinsi Gotland. Visby tower wall Pranala luar Wikimedia Commons memiliki media mengenai Hansestaden Visby.

Philip Dorsheimer

American politician Philip DorsheimerNew York State TreasurerIn office1860–1861GovernorEdwin D. MorganPreceded byIsaac V. VanderpoelSucceeded byWilliam B. Lewis Personal detailsBorn(1797-04-15)April 15, 1797Wöllstein, GermanyDiedApril 11, 1868(1868-04-11) (aged 70)Buffalo, New YorkPolitical partyDemocratic PartyRepublican Party (upon its formation in 1854)Spouse Sarah Gorgas ​ ​(m. 1821; died 1867)​ChildrenWilliam Dorsheimer Philip Dorsh...

 

 

Gilleleje railway station

Railway station in Gilleleje, Denmark Gillelejerailway stationFront facade of Gilleleje stationGeneral informationLocationGilleleje Stationsvej 103250 Gilleleje[1][2]Gribskov MunicipalityDenmarkCoordinates56°07′25″N 12°18′11″E / 56.1237°N 12.3030°E / 56.1237; 12.3030Elevation8.5 metres (28 ft)[3]Owned byHovedstadens LokalbanerOperated byLokaltog[4]Line(s)Hornbæk Line Gribskov LinePlatforms2Tracks3ConstructionArchitectHe...

 

 

Roger Kwok

Hong Kong actor Roger Kwok郭晋安Born (1964-10-09) October 9, 1964 (age 59)Cheung Chau, Hong KongOccupation(s)Actor, SingerYears active1986–presentNotable workSquare Pegs Life Made Simple Black Heart White Soul Big White Duel seriesSpouseCindy Au (m. 2006-2024)Children2 (Son: Brad Kwok Ling-shan, Daughter: Blair Kwok Yee-nga)AwardsTVB Anniversary Awards – Best Actor2003 Square Pegs2005 Life Made Simple2014 Black Heart White Soul TVB Star Awards Malaysia – Favourite TVB Actor...

Giovanni Battista Re

Giovanni Battista RePrefek Emeritus Kongregasi bagi Uskup-uskupPenunjukan16 September 2000Masa jabatan berakhir30 Juni 2010PendahuluLucas Moreira NevesPenerusMarc OuelletJabatan lainKardinal-Uskup Sabina-Poggio MirtetoImamatTahbisan imam3 Maret 1957oleh Giacinto TrediciTahbisan uskup7 November 1987oleh Paus Yohanes Paulus IIPelantikan kardinal21 Februari 2001oleh Paus Yohanes Paulus IIPeringkatKardinal-Imam (2001-2002) Kardinal-Uskup (2002-sekarang)Informasi pribadiLahir30 Januari 1...

 

 

Протаскивание под килем

Для термина «килевание» см. также другие значения. Протаскивание под килем в период Тюдоров (1485—1603) «Протаскивание под килем корабельного хирурга адмирала Яна Ван Неса», картина Ливе Питерсзона Версхюра Прота́скивание под ки́лем (килевание) — в эпоху парусных судов �...

 

 

N-02D

NTTドコモ N-02D 開いた状態 閉じた状態 キャリア NTTドコモ 製造 NECカシオ モバイルコミュニケーションズ 発売日 2011年12月16日 概要 OS Access Linux Platform + OPP(L) CPU OMAP 3430 音声通信方式 3G：FOMA（W-CDMA）2G：GSM（3G：800MHz、850MHz、1.7GHz、2GHz) (2G：900MHz、1800MHz、1900MHz） データ通信方式 3G：FOMA（HSDPA・HSUPA）2G：GSM 形状 防水2軸折りたたみ型 サイズ 112 × 51 × 12.9 （最厚部約 1...

1748

1748 – MDCCXLVIII276 år sedan År1745 | 1746 | 174717481749 | 1750 | 1751 Årtionde1720-talet  | 1730-talet 1740-talet1750-talet | 1760-talet Århundrade1600-talet 1700-talet1800-talet Årtusende1000-talet Året Födda | AvlidnaBildanden | Upplösningar Humaniora och kulturKonst, litteratur, musik och teater Samhällsvetenskapoch samhälleKrig Teknik och vetenskap Vetenskap Andra tideräkningar Gregoriansk...

 

 

成田蓮

この存命人物の記事には検証可能な出典が不足しています。 信頼できる情報源の提供に協力をお願いします。存命人物に関する出典の無い、もしくは不完全な情報に基づいた論争の材料、特に潜在的に中傷・誹謗・名誉毀損あるいは有害となるものはすぐに除去する必要があります。出典検索?: 成田蓮 – ニュース · 書籍 · スカラー · CiNii · ...