Solution Structure of the Catalytic Domain of Human Stromelysin-1 Complexed to a Potent, Nonpeptidic Inhibitor

Biochemistry ◽  
1998 ◽  
Vol 37 (40) ◽  
pp. 14048-14056 ◽  
Author(s):  
Yu-Chin Li ◽  
Xiaolu Zhang ◽  
Richard Melton ◽  
Vishwas Ganu ◽  
Nina C. Gonnella
Keyword(s):  
Solution Structure ◽  
Catalytic Domain

scholarly journals Solution structure of the catalytic domain of human stromelysin complexed with a hydrophobic inhibitor

1995 ◽  
Vol 4 (12) ◽  
pp. 2487-2498 ◽  
Author(s):  
Steven R. Van Doren ◽  
Alexander V. Kurochkin ◽  
Weidong Hu ◽  
Qi-Zhuang Ye ◽  
Linda L. Johnson ◽  
...  
Keyword(s):  
Solution Structure ◽  
Catalytic Domain

scholarly journals Solution structure of the N-terminal catalytic domain of human H-REV107 - A novel circular permutated NlpC/P60 domain

FEBS Letters ◽  
2010 ◽  
Vol 584 (19) ◽  
pp. 4222-4226 ◽  
Author(s):  
Xiaobai Ren ◽  
Jian Lin ◽  
Changwen Jin ◽  
Bin Xia
Keyword(s):  
Solution Structure ◽  
Catalytic Domain

Solution structure of the catalytic domain of γδ resolvase. Implications for the mechanism of catalysis 1 1Edited by P. E. Wright

2001 ◽  
Vol 310 (5) ◽  
pp. 1089-1107 ◽  
Author(s):  
Borlan Pan ◽  
Mark W Maciejewski ◽  
Assen Marintchev ◽  
Gregory P Mullen
Keyword(s):  
Solution Structure ◽  
Catalytic Domain ◽  
Mechanism Of Catalysis

Solution structure of the catalytic domain of RICH protein from goldfish

FEBS Journal ◽  
2007 ◽  
Vol 274 (6) ◽  
pp. 1600-1609 ◽  
Author(s):  
Guennadi Kozlov ◽  
Alexey Y. Denisov ◽  
Ekaterina Pomerantseva ◽  
Michel Gravel ◽  
Peter E. Braun ◽  
...  
Keyword(s):  
Solution Structure ◽  
Catalytic Domain

Solution structure and DNA binding of the catalytic domain of the large serine resolvase TnpX

2015 ◽  
Vol 28 (5) ◽  
pp. 316-324 ◽  
Author(s):  
Stephen J. Headey ◽  
Andrew Sivakumaran ◽  
Vicki Adams ◽  
Dena Lyras ◽  
Julian I. Rood ◽  
...  
Keyword(s):  
Dna Binding ◽  
Solution Structure ◽  
Catalytic Domain

Solution structure of the Cys74 to Ala74 mutant of the recombinant catalytic domain of Zoocin A

2016 ◽  
Vol 85 (1) ◽  
pp. 177-181 ◽  
Author(s):  
Minli Xing ◽  
Robin S. Simmonds ◽  
Russell Timkovich
Keyword(s):  
Solution Structure ◽  
Catalytic Domain ◽  
Zoocin A

scholarly journals Solution Structure of the MAPK Phosphatase PAC-1 Catalytic Domain

Structure ◽  
2003 ◽  
Vol 11 (2) ◽  
pp. 155-164 ◽  
Author(s):  
Amjad Farooq ◽  
Olga Plotnikova ◽  
Gaurav Chaturvedi ◽  
Sherry Yan ◽  
Lei Zeng ◽  
...  
Keyword(s):  
Solution Structure ◽  
Catalytic Domain ◽  
Mapk Phosphatase

A Cyclic Pentapeptide Derived from the Second EGF-Like Domain of Factor VII Is an Inhibitor of Tissue Factor Dependent Coagulation and Thrombus Formation

2002 ◽  
Vol 87 (01) ◽  
pp. 13-21 ◽  
Author(s):  
Peter Fischer ◽  
Chih-Kao Hu ◽  
Erik Agner ◽  
May Engebretsen ◽  
Mette Husbyn ◽  
...  
Keyword(s):  
Complex Formation ◽  
Solution Structure ◽  
Catalytic Domain ◽  
Cyclic Peptide ◽  
Ex Vivo ◽  
Thrombus Formation ◽  
Anticoagulant Activity ◽  
Factor Vii ◽  
Fibrin Adhesion ◽  
Ic50 Values

SummaryWe have previously reported the finding of a cyclic dodecapeptide representing loop I of the second EGF-like domain of FVII, which inhibited TF-dependent FX activation (Örning et al. 1997). The biological activity was localized to the tripeptide motif, Glu-Gln-Tyr. We have now synthesized a cyclic analog of this motif, Cys-Glu-Gln-Tyr-Cys (PN7051), evaluated its anticoagulant and antithrombotic properties and performed a detailed structural characterization of the peptide.PN7051 is a dose-dependent inhibitor of TF-dependent FX activation and coagulation of plasma with IC50 values of 10 ± 2 µM and 1.3 ± 0.2 mM, respectively. It shows inhibitory efficacy on acute thrombus formation in an ex vivo model of human thrombosis using native blood. Fibrin deposition, platelet-fibrin adhesion, platelet-thrombus formation, and thrombin-antithrombin complex formation were all inhibited by PN7051 at IC50 values between 0.3 and 0.7 mM. The cyclic peptide is a non-competitive inhibitor of FX activation with no significant activesite effects on FXa or FVIIa, indicating it affects FVII/TF/FX complex formation and function. Studies on the structure activity relationship revealed that Gln3-Tyr4, but not Glu2 were of importance for inhibition. In line with biological results, NMR measurements of PN7051 suggested that the Gln and Tyr residues configure a structural feature that contributes to the anticoagulant activity. Modeling of the Glu99Gln100Tyr101 motif in FVII and comparison with the solution structure of PN7051 suggest that the cyclic pentapeptide exerts its antithrombotic effect by interfering with the docking of Tyr101 into a hydrophobic pocket in the catalytic domain thereby disrupting an essential interaction between the second EGF-like and the catalytic domains of FVII.

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