Thumbnail
Access Restriction
Open

Author Kadono, Shojiro ♦ Sakamoto, Akihisa ♦ Kikuchi, Yasufumi ♦ Oh-Eda, Masayoshi ♦ Yabuta, Naohiro ♦ Koga, Takaki ♦ Hattori, Kunihiro ♦ Shiraishi, Takuya ♦ Haramura, Masayuki ♦ Kodama, Hirofumi ♦ Ono, Yoshiyuki ♦ Esaki, Toru ♦ Sato, Haruhiko ♦ Watanabe, Yoshiaki ♦ Itoh, Susumu ♦ Ohta, Masateru ♦ Kozono, Toshiro
Source World Health Organization (WHO)-Global Index Medicus
Content type Text
Publisher Wiley
File Format HTM / HTML
Language English
Difficulty Level Medium
Subject Domain (in DDC) Natural sciences & mathematics ♦ Chemistry & allied sciences ♦ Crystallography ♦ Life sciences; biology ♦ Physiology & related subjects ♦ Biochemistry ♦ Natural history of organisms ♦ Technology ♦ Medicine & health ♦ Human physiology ♦ Pharmacology and therapeutics ♦ Diseases ♦ Manufacture for specific uses ♦ Precision instruments & other devices
Subject Domain (in MeSH) Eukaryota ♦ Organisms ♦ Macromolecular Substances ♦ Enzymes and Coenzymes ♦ Amino Acids, Peptides, and Proteins ♦ Chemical Actions and Uses ♦ Chemicals and Drugs ♦ Investigative Techniques ♦ Analytical, Diagnostic and Therapeutic Techniques and Equipment ♦ Chemical Phenomena ♦ Circulatory and Respiratory Physiological Phenomena ♦ Biological Sciences
Subject Keyword Discipline Crystallography ♦ Discipline Biophysics ♦ Discipline Molecular Biology ♦ Discipline Biochemistry ♦ Anticoagulants ♦ Chemistry ♦ Factor Viia ♦ Antagonists & Inhibitors ♦ Thromboplastin ♦ Antithrombins ♦ Blood Coagulation ♦ Crystallography, X-ray ♦ Drug Design ♦ Humans ♦ Macromolecular Substances ♦ Models, Molecular ♦ Peptides ♦ Protein Structure, Secondary ♦ Journal Article
Abstract The crystal structure of human factor VIIa/soluble tissue factor (FVIIa/sTF) in complex with a highly selective peptide-mimetic FVIIa inhibitor which shows 1670-fold selectivity against thrombin inhibition has been solved at 2.6 A resolution. The inhibitor is bound to FVIIa/sTF at the S1, S2 and S3 sites and at the additional S1 subsite. Two charged groups, the amidino group in P2 and the carboxylate group in P4, form ionic interactions with Asp60 and Lys192 of FVIIa, respectively. Structural comparisons between factor VIIa and thrombin show that thrombin has oppositely charged residues, Lys60F and Glu192, in the S2 site and the S1 subsites, respectively. These data suggest that the utilization of the differences of charge distribution in the S2 site and the S1 subsites between FVIIa and thrombin is critical for achieving high selectivity against thrombin inhibition. These results will provide valuable information for the structure-based drug design of specific inhibitors for FVIIa/TF.
Description Country affiliation: Japan
Author Affiliation: Kadono S ( Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co. Ltd, 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan. kadonosuj@chugai-pharm.co.jp)
ISSN 2053230X
Educational Role Student ♦ Teacher
Age Range above 22 year
Educational Use Reading ♦ Research ♦ Self Learning
Interactivity Type Expositive
Education Level UG and PG
Learning Resource Type Article
Publisher Date 2005-02-01
Publisher Place Great Britain (UK)
e-ISSN 17443091
Journal Acta Crystallographica Section F Structural Biology and Crystallization Communications
Volume Number 61
Issue Number Pt 2


Source: WHO-Global Index Medicus