3c1k: Difference between revisions

Revision as of 21:17, 4 May 2008

Crystal structure of thrombin in complex with inhibitor 15

OverviewOverview

Guided by X-ray crystallography of thrombin-inhibitor complexes and molecular modeling, alkylation of the N1 nitrogen of the imidazole P1 ligand of the pyridinoneacetamide thrombin inhibitor 1 with various acetamide moieties furnished inhibitors with significantly improved thrombin potency, trypsin selectivity, functional in vitro anticoagulant potency and in vivo antithrombotic efficacy. In the pyrazinoneacetamide series, oral bioavailability was also improved.

About this StructureAbout this Structure

3C1K is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Structure-based design of novel groups for use in the P1 position of thrombin inhibitor scaffolds. Part 2: N-acetamidoimidazoles., Isaacs RC, Solinsky MG, Cutrona KJ, Newton CL, Naylor-Olsen AM, McMasters DR, Krueger JA, Lewis SD, Lucas BJ, Kuo LC, Yan Y, Lynch JJ, Lyle EA, Bioorg Med Chem Lett. 2008 Mar 15;18(6):2062-6. Epub 2008 Jan 30. PMID:18291642 Page seeded by OCA on Sun May 4 21:17:16 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:3c1k.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 3c1k |SIZE=350|CAPTION= <scene name='initialview01'>3c1k</scene>, resolution 1.84&Aring;
+The line below this paragraph, containing "STRUCTURE_3c1k", creates the "Structure Box" on the page.
-|SITE= <scene name='pdbsite=AC1:T15+Binding+Site+For+Residue+A+403'>AC1</scene>
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=T15:2-{3-[(BENZYLSULFONYL)AMINO]-6-METHYL-2-OXOPYRIDIN-1(2H)-YL}-N-({1-[2-(TERT-BUTYLAMINO)-2-OXOETHYL]-4-METHYL-1H-IMIDAZOL-5-YL}METHYL)ACETAMIDE'>T15</scene>, <scene name='pdbligand=TYS:SULFONATED+TYROSINE'>TYS</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|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>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=<span class='plainlinks'>[http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=pfam09396 Thrombin_light], [http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=cd00190 Tryp_SPc]</span>
+{{STRUCTURE_3c1k|  PDB=3c1k  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3c1k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3c1k OCA], [http://www.ebi.ac.uk/pdbsum/3c1k PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=3c1k RCSB]</span>
-}}
 '''Crystal structure of thrombin in complex with inhibitor 15'''
@@ Line 27: / Line 24: @@
 [[Category: Thrombin]]
 [[Category: Yan, Y.]]
-[[Category: acute phase]]
+[[Category: Acute phase]]
-[[Category: blood coagulation]]
+[[Category: Blood coagulation]]
-[[Category: calcium]]
+[[Category: Calcium]]
-[[Category: cleavage on pair of basic residue]]
+[[Category: Cleavage on pair of basic residue]]
-[[Category: disease mutation]]
+[[Category: Disease mutation]]
-[[Category: gamma-carboxyglutamic acid]]
+[[Category: Gamma-carboxyglutamic acid]]
-[[Category: glycoprotein]]
+[[Category: Glycoprotein]]
-[[Category: hydrolase]]
+[[Category: Hydrolase]]
-[[Category: kringle]]
+[[Category: Kringle]]
-[[Category: pharmaceutical]]
+[[Category: Pharmaceutical]]
-[[Category: polymorphism]]
+[[Category: Polymorphism]]
-[[Category: protease]]
+[[Category: Protease]]
-[[Category: protease inhibitor]]
+[[Category: Protease inhibitor]]
-[[Category: secreted]]
+[[Category: Secreted]]
-[[Category: serine protease]]
+[[Category: Serine protease]]
-[[Category: serine protease inhibitor]]
+[[Category: Serine protease inhibitor]]
-[[Category: sulfation]]
+[[Category: Sulfation]]
-[[Category: thrombin]]
+[[Category: Thrombin]]
-[[Category: thrombin inhibitor complex]]
+[[Category: Thrombin inhibitor complex]]
-[[Category: zymogen]]
+[[Category: Zymogen]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 21:17:16 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr  2 11:32:48 2008''