Disintegrins: The Challenge of Nomenclature Mary Ann McLane University of Delaware ISTH Subcommittee...
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Transcript of Disintegrins: The Challenge of Nomenclature Mary Ann McLane University of Delaware ISTH Subcommittee...
Disintegrins:The Challenge of Nomenclature
Mary Ann McLaneUniversity of Delaware
ISTH Subcommittee on Exogenous Hemostatic FactorsAugust 6, 2005
Snake venom proteins active on the hemostatic system (Markland 1998)
Factor V activating Factor X activating Factor IX activating Prothrombin
activating Fibrinogen clotting Protein C activating Factor IX/factor X-
binding protein Thrombin inhibitor
Phospholipase A Fibrin(ogen)
degradation Plasminogen activation Hemorrhagic Platelet aggregation
inducers Inhibitors of platelet
aggregation Inhibitors of serpins
Snake venom proteins active on the hemostatic system (Markland 1998)
Factor V activatingFactor V activating Factor X activatingFactor X activating Factor IX activatingFactor IX activating Prothrombin
activating Fibrinogen clotting Protein C activating Factor IX/factor X-
binding protein Thrombin inhibitor
Phospholipase APhospholipase A Fibrin(ogen) Fibrin(ogen)
degradationdegradation Plasminogen activationPlasminogen activation HemorrhagicHemorrhagic Platelet aggregation Platelet aggregation
inducersinducers Inhibitors of platelet Inhibitors of platelet
aggregationaggregation Inhibitors of serpinsInhibitors of serpins
1991,2000 “-arin” or “activase” added to
prefixes derived from Latin species name, plus designation of A, B, C or D based on cofactor requirements
Snake venom proteins active on the hemostatic system (Markland 1998)
Factor V activatingFactor V activating Factor X activatingFactor X activating Factor IX activatingFactor IX activating Prothrombin Prothrombin
activatingactivating Fibrinogen clottingFibrinogen clotting Protein C activatingProtein C activating Factor IX/factor X-Factor IX/factor X-
binding proteinbinding protein Thrombin inhibitorThrombin inhibitor
Phospholipase APhospholipase A Fibrin(ogen) Fibrin(ogen)
degradationdegradation Plasminogen activationPlasminogen activation HemorrhagicHemorrhagic Platelet aggregation Platelet aggregation
inducersinducers Inhibitors of platelet
aggregation Inhibitors of serpinsInhibitors of serpins
Disintegrins: 80% “-in”
Disintegrins: 43% “-in” Halysin Salmosin Applagin Kistrin Gabonin, 1, 2 Bothrasperin Cotiarin Jararacin Rhodostomin Crotatoxin Basilicin Durissin Molossin Crotavirin
Cereberin Lutosin Viridin Pyramidin Eristocophin Brevicaudin 1a, 1b, 2b Saxatilin Lachesin Tergeminin Barbourin Alblabrin Falvoridin Triflavin Trigramin
Disintegrins: 36% “-tin” Halystatin Accutin Contortrostatin Acostatin Halysetin Piscivostatin Ussuristatin 1, 2 Bitistatin Arietin Batroxostatin Jarastatin Cerastatin
Cerastin Schistatin Echistatin leukogastinA, B Multisquamatin Ocellatin Eristostatin Elegantin Flavostatin Trimestatin Jerdonatin Obtustatin Viperostatin
Disintegrins: “-statin” Halystatin AccutinAccutin Contortrostatin Acostatin HalysetinHalysetin Piscivostatin Ussuristatin 1, 2 Bitistatin ArietinArietin Batroxostatin Jarastatin Cerastatin
CerastinCerastin Schistatin Echistatin leukogastinA, BleukogastinA, B MultisquamatinMultisquamatin OcellatinOcellatin Eristostatin ElegantinElegantin Flavostatin Trimestatin JerdonatinJerdonatin Obtustatin Viperostatin
Disintegrins: 17% “EF#”
CC5 CC8 EMS11 EC3 EC6 EO4
EO5 EMF10 VA6 VB7 VLO4 VLO5
Disintegrins: 3% “acronym#”
CTF-I CTF-II
Disintegrins: 1% “-or”
adinbitor
Disintegrins since 2004
Jerdonin (Trimeresurus jerdonii)
Bothrostatin (Bothrops jararaca)
Total = 75
Note: No information from the name about whether the protein is a monomer
or dimer
Standardizing nomenclature
Realities “statin” = suffix used for naming class of
HMG-CoA reductase inhibitors for controlling cholesterol levels
Lipitor (atorvastatin) - Pfizer Zocor (simvastatin) - Merck Pravachol (pravastatin) - Bristol-Myers Squibb Lescol (fluvastatin) - Novartis Mevacor (lovastatin) - Merck Crestor (rosuvastatin) - AstraZeneca
Standardizing nomenclature
Realities Subspecies discoveries
Echis…. Echistatin Echistatin Echistatin
Standardizing nomenclature
Realities Subspecies discoveries http://www.embl-heidelberg.de
Echis carinatus Echistatin
Echis carinatus sochurecki
Echis sochurecki
1969
1999 2001
Standardizing nomenclature Realities
Genus different, species the same carinatin [Tropidechis carinatus]
Non-disintegrin carinatin [Echis carinatus]
Echistatin 2
http://www.kingsnake.com/oz/snakes/elapids/tcarinata.htm
http://itgmv1.fzk.de/www/itg/uetz/herp/photos/Echis_carinatus2.jpg
Standardizing nomenclature
Realities Genus same, species the same,
different proteins discovered Echistatin Schistatin Carinatin EC3
Standardizing nomenclature
Recommendation Disintegrins prior to 2004 = retain name This standardization committee will
determine how many proteins have been discovered from each genus-species-subspecies (to get the next number)
Include the NCBI protein database http://www.ncbi.nlm.nih.gov/entrez for disintegrins named after cDNA analysis
Standardizing nomenclature
Recommendation New disintegrins are named by
combination of genus-subspecies or species-subspecies Latin name followed by “-min” for monomer or “din” for dimers
Numbered sequentially from that point on
Standardizing nomenclature
Echis carinatus sochurecki Echistatin EC3 EC6 Schistatin Ecarisomin 5 (a monomer)
Standardizing nomenclature
Echis carinatus sochurecki Echistatin EC3 EC6 Schistatin Ecarisomin 5 (a monomer) Ecarisodin 6 (a dimer) Ecarisotin 7 (unsure of structure; cDNA name)
Standardizing nomenclature
Gloydius genus Gloydius blomhoffi brevicaudus
Adinbitor Blobrevidin 2 (a dimer)
Gloydius halys brevicaudus Brevicaudin 1a, 1b, 2b Halybrevimin 4 (a monomer)
Gloydius saxatilis Saxitilin Gloysaxatin 2 (unknown structure)
Standardizing nomenclature
More realities Does not eliminate potential confusion when
genus names change Agkistrodon rhodostoma (1930)
Kistrin (Dennis 1990) Calloselasma rhodostoma (1827, 1994)
Rhodostomin (Au 1991)
“-cetin” is also used for naming C-lectin-like proteins targeting GPIb, GPVI and/or 21
Discussion!