3bv9

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[[Image:3bv9.jpg|left|200px]]
[[Image:3bv9.jpg|left|200px]]
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{{Structure
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<!--
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|PDB= 3bv9 |SIZE=350|CAPTION= <scene name='initialview01'>3bv9</scene>, resolution 1.80&Aring;
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The line below this paragraph, containing "STRUCTURE_3bv9", creates the "Structure Box" on the page.
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|SITE= <scene name='pdbsite=AC1:Oic+Binding+Site+For+Residue+C+402'>AC1</scene>, <scene name='pdbsite=AC2:4ph+Binding+Site+For+Residue+C+405'>AC2</scene>, <scene name='pdbsite=AC3:Iod+Binding+Site+For+Residue+B+303'>AC3</scene>, <scene name='pdbsite=AC4:Na+Binding+Site+For+Residue+B+307'>AC4</scene>, <scene name='pdbsite=AC5:Nh2+Binding+Site+For+Residue+C+406'>AC5</scene> and <scene name='pdbsite=AC6:Gol+Binding+Site+For+Residue+B+305'>AC6</scene>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=4PH:4-METHYL-L-PHENYLALANINE'>4PH</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=DAR:D-ARGININE'>DAR</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=OIC:OCTAHYDROINDOLE-2-CARBOXYLIC+ACID'>OIC</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] </span>
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or leave the SCENE parameter empty for the default display.
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|GENE= F2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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|DOMAIN=<span class='plainlinks'>[http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=cd00190 Tryp_SPc]</span>
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{{STRUCTURE_3bv9| PDB=3bv9 | SCENE= }}
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|RELATEDENTRY=[[1sfq|1SFQ]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3bv9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bv9 OCA], [http://www.ebi.ac.uk/pdbsum/3bv9 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=3bv9 RCSB]</span>
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}}
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'''Structure of Thrombin Bound to the Inhibitor FM19'''
'''Structure of Thrombin Bound to the Inhibitor FM19'''
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[[Category: Warnock, M.]]
[[Category: Warnock, M.]]
[[Category: Zhou, Y.]]
[[Category: Zhou, Y.]]
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[[Category: acute phase]]
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[[Category: Acute phase]]
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[[Category: blood coagulation]]
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[[Category: Blood coagulation]]
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[[Category: calcium]]
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[[Category: Calcium]]
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[[Category: cleavage on pair of basic residue]]
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[[Category: Cleavage on pair of basic residue]]
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[[Category: disease mutation]]
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[[Category: Disease mutation]]
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[[Category: gamma-carboxyglutamic acid]]
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[[Category: Gamma-carboxyglutamic acid]]
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[[Category: glycoprotein]]
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[[Category: Glycoprotein]]
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[[Category: hydrolase]]
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[[Category: Hydrolase]]
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[[Category: kringle]]
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[[Category: Kringle]]
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[[Category: polymorphism]]
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[[Category: Polymorphism]]
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[[Category: secreted]]
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[[Category: Secreted]]
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[[Category: serine protease]]
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[[Category: Serine protease]]
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[[Category: zymogen]]
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[[Category: Zymogen]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 21:08:46 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 2 11:32:50 2008''
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Revision as of 18:08, 4 May 2008

Image:3bv9.jpg

Template:STRUCTURE 3bv9

Structure of Thrombin Bound to the Inhibitor FM19


Contents

Overview

Background: Novel pentapeptides called Thrombostatin FM compounds consisting mostly of D-isomers and unusual amino acids were prepared based upon the stable angiotensin converting enzyme breakdown product of bradykinin - RPPGF. Methods and Results: These peptides are direct thrombin inhibitors prolonging the thrombin clotting time, APTT, and PT at >/= 0.78, 1.6 and 1.6 muM, respectively. They competitively inhibit alpha-thrombin-induced cleavage of a chromogenic substrate at 4.4-8.2 muM. They do not significantly inhibit plasma kallikrein, FXIIa, FXIa, FIXa, FVIIa-TF, FXa, plasmin or cathepsin G. One form, FM19 [rOicPaF(p-Me)], blocks alpha-thrombin induced calcium flux in fibroblasts with an IC(50) of 6.9 +/- 1.2 muM. FM19 achieved 100% inhibition of threshold alpha- or gamma-thrombin-induced platelet aggregation at 8.4 +/- 4.7 muM and 16 +/- 4 muM, respectively. The crystal structure of thrombin in complex with FM19 shows that the N-terminal D-Arg retrobinds into the S1 pocket, its 2nd residue Oic interacts with His-57, Tyr-60a and Trp-60d, and its C-terminal p-methyl Phe engages thrombin's aryl binding site composed of Ile-174, Trp-215 and Leu-99. When administered intraperitoneal, intraduodenal, or orally to mice, FM19 prolongs thrombin clotting times and delays carotid artery thrombosis. Conclusion: FM19, a low affinity reversible direct thrombin inhibitor, might be useful as an add-on agent to address an unmet need in platelet inhibition in acute coronary syndromes in diabetics and others who with all current anti-platelet therapy still have reactive platelets.

Disease

Known disease associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]

About this Structure

3BV9 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Thrombostatin FM compounds: direct thrombin inhibitors - mechanism of action in vitro and in vivo., Nieman MT, Burke F, Warnock M, Zhou Y, Sweigart J, Chen A, Ricketts D, Lucchesi BR, Chen Z, Di Cera E, Hilfinger J, Kim JS, Mosberg HI, Schmaier AH, J Thromb Haemost. 2008 Feb 25;. PMID:18315550 Page seeded by OCA on Sun May 4 21:08:46 2008

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OCA

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