1997 MINUTES
REGISTRY OF EXOGENOUS HEMOSTATIC FACTORS SUBCOMMITTEE
Monday, 9 June, 1997, 2:30-5:30
Vasari, Fortezza da Basso
Florence, Italy
Chair: F. Markland, USA
Co-Chair: N. Marsh, Australia
Seven members of the registry were in attendance plus about 8-15 guests.
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Welcome: |
Francis S. Markland, Chair |
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N. Marsh, Co-chair |
Introduction of new member of the registry: Dr. Carmen Arocha-Pinango
Outline of the program:
Reports on Inventories
New Business
Next Meeting
Change of Chairmanship
Reports on Inventories
Dr. Pirkle was unable to attend to present his updated inventory of venom thrombin-like enzymes (TLEs), but his remarks were given by Dr. Markland.
There are eight amino acid sequences of thrombin-like enzymes that have been determined and they were presented as a figure. All share active site residues H57, D102, and S195 (the numbering of the sequences for all these enzymes is based on that of chymotrypsinogen). One problem is with ancrod for which two sequences have been reported. One derived from cDNA and the other chemically determined. There is a high degree of difference between the two sequences owing to the fact that the cDNA sequence was determined from a probe directed to the amino-terminal end of the protein, thereby producing potential ambiguities. All 12 half-cystine residues aligned perfectly. Carbohydrate content in TLEs varies widely. Reclassification of A. rhodostoma to C. rhodostoma seems accurate based on recent evidence. A table of all the thrombin-like enzymes and various properties were presented. A motion was made to submit this report to the SSC for publication. The motion was seconded and approved.
Dr. Markland updated the inventory of fibrinogenolytic and fibrinolytic enzymes.
He discussed seven groups based on the snake families from which the enzymes are derived. The grouping is further broken down into geographical areas. Sixty-five enzymes were described. One plasminogen activator was additionally reported. The metalloproteinases, which are mainly Aa-chain preferring, all show structural homology. An example was shown, using the predicted structure of fibrolase, which has the metzincin motif in the active site. Tables showing the properties and cleavage specificity were presented to the registry. A major change from the past inventory was a reclassification of the enzymes based on snake family and geography rather than on chain cleavage. Additionally, a number of serine proteinases with fibrino(geno)lytic activity directed primarily to the Bb-chain were reported. One suggestion was to indicate that the enzymes presented are direct-acting agents. A motion was made to submit the report to the SSC for publication and the motion was seconded and approved.
Dr. Brinkhous was not present and has resigned from the registry. Thus, his report on platelet aggregating agents was not presented.
Dr. Teng described factors affecting platelet aggregation.
These are arranged according to activities into four different groups: GPIIb-IIIa antagonists, collagen platelet interactive agents, non-coagulant non-enzymatic inducers of platelet aggregation, and effectors of vWF-GPIb interaction. Additionally, sources of platelet aggregation factors from plants were presented and these were arranged into 12 groups based on activity. Dr. Teng desires not to update his inventory at this time and this was accepted by the chair.
Dr. Arocha-Pinango described hemostatic activities of arthropods.
Dr. Arocha-Pinango stated that the information is very scattered and there are very few well-characterized agents but those that have been identified are divided into five groups. The first are effectors of thrombin-fibrinogen interaction. There are those that act on platelets and in this group there is a single agent which is an inducer of aggregation. Prothrombin activators are not well-characterized. Fibrinolytic agents are mostly identified as plasminogen activators, but no further information is known. Lastly, a large number of enzymes fall into the category of miscellaneous unclassified agents of unknown mode of action. Many of the papers describing these agents were published a number of years ago, and additional information is unavailable. A motion was made to submit Dr. Arocha-Pinango's report for publication to the SSC and this motion was seconded and approved.
New Business
The chair called for recommendations for replacement of Dr. Brinkhous. One recommendation was previously received and another was suggested from the floor. The new member of the registry will be appointed by the new chairman.
Next Meeting
It was proposed that the next meeting of the registry take place in Washington, DC, in 1999, unless any pressing matters arise between now and then. The inventories in need of updating at the next meeting are Platelet Aggregation Agents, an inventory of bacterial fibrinolytic agents, and an inventory of snake venom hemorrhagic proteins.
Change of Chairmanship
This meeting concludes Dr. Markland's term of chairmanship. Dr. Marsh thanked Dr. Markland for his service as chairman. The meeting was then adjourned at 5 p.m.