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Volume 10
Journal of Blood Disorders & Transfusion
ISSN: 2155-9864
Hematology Congress 2019
March 18-19, 2019
conference
series
.com
March 18-19, 2019 | Rome, Italy
16
th
World Hematology Congress
Page 22
Igor Križaj, J Blood Disord Transfus 2019, Volume 10
DOI: 10.4172/2155-9864-C1-039
The first intrinsic tenase complex inhibitor with serine protease structure: A new perspective in
anticoagulant therapy
C
omponents of the intrinsic blood coagulation pathway, among them factor VIIIa (FVIIIa), have been recognized
as suitable therapeutic targets to treat venous thromboembolism, pathological process behind two very serious
cardiovascular diseases, deep vein thrombosis and pulmonary embolism. Here, we describe a unique glycoprotein from
the nose-horned viper (
Vipera ammodytes ammodytes
[Vaa]) venom, Vaa serine proteinase homolog 1 (VaaSPH-1),
structurally a serine protease but without an enzymatic activity and expressing potent anticoagulant action in human
blood. We demonstrated that one of its targets in the blood coagulation system is FVIIIa of the intrinsic tenase complex,
where it antagonizes the binding of FIXa. Anticoagulants with such characteristics are intensively sought, as they would
be much safer for medical application as the contemporary drugs, which frequently induce excessive bleeding and other
complications. VaaSPH-1 is unlikely to be orally available for chronic usage as it has molecular mass of 35 kDa. However,
it represents a very promising template to design low molecular mass FVIIIa-directed anticoagulant substances, based
on structural features of the interaction surface between VaaSPH-1 and FVIIIa. To this end, we constructed a three-
dimensional model of VaaSPH-1 bound to FVIIIa. The model exposes the 157-loop and the preceding α-helix as the
most appropriate structural elements of VaaSPH-1 to be considered as a guideline to synthesize small FVIIIa-binding
molecules, potential new generation of anticoagulants.
Biography
He is Professor and Scientific Counsellor at Department of Molecular and Biomedical Sciences, Jozef Stefan Institute, Slovenia. Expert evaluator for the
Slovenian Ministry of Higher Education, Science and Technology. Reviewer at Brain Research, Biological Chemistry, Biochimie, Comparative Biochemistry and
Physiology, Biochemical Pharmacology, Research in Microbiology, FEBS Letters, FEBS Journal, The Canadian Journal ofAnalytical Sciences and Spectroscopy,
Cellular and Molecular Biology Letters, Journal of Controlled Release, The Protein Journal, The Journal of Molecular Evolution, Thomson Reuters' Drug Profiles,
Procedia Chemistry, Journal of Neurochemistry, Molecular Neurobiology, Journal of Proteome Research, PLOS Neglected Tropical Diseases.
igor.krizaj@ijs.siIgor Krizaj
Jozef Stefan Institute, Slovenia