3vf8: Difference between revisions

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-[[Image:3vf8.jpg|left|200px]]
+==Crystal Structure of Spleen Tyrosine Kinase Syk Catalytic Domain with Pyrazolylbenzimidazole Inhibitor 416==
+<StructureSection load='3vf8' size='340' side='right' caption='[[3vf8]], [[Resolution|resolution]] 2.08&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3vf8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VF8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VF8 FirstGlance]. <br>
+</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0JE:3-[5-(5-ETHOXY-6-FLUORO-1H-BENZIMIDAZOL-2-YL)-1H-PYRAZOL-4-YL]-1,1-DIETHYLUREA'>0JE</scene><br>
+<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3vf9|3vf9]], [[3v5l|3v5l]], [[3v5j|3v5j]], [[3v8w|3v8w]]</td></tr>
+<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SYK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>
+<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3vf8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vf8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3vf8 RCSB], [http://www.ebi.ac.uk/pdbsum/3vf8 PDBsum]</span></td></tr>
+<table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Beginning with a screening hit, unique thienopyrazole-indole inhibitors of Itk (interleukin-2-inducible tyrosine kinase) were designed, synthesized, and crystallized in the target kinase. Although initial compounds were highly active in Itk, they were not selective. Increasing the steric bulk around a tertiary alcohol at the 5-indole position dramatically improved selectivity toward Lyk and Syk, but not Txk. Substitutions at the 3- and 4-indole positions gave less active compounds that remained poorly selective. A difluoromethyl substitution at the 5-position of the thienopyrazole led to a highly potent and selective compound. Phenyl at this position reduced activity and selectivity while pushing the side-chains of Lys-391 and Asp-500 away from the binding pocket. Novel and selective thienopyrazole inhibitors of Itk were designed as a result of combining structure-based design and medicinal chemistry.
-<!--
+X-ray crystallographic structure-based design of selective thienopyrazole inhibitors for interleukin-2-inducible tyrosine kinase.,McLean LR, Zhang Y, Zaidi N, Bi X, Wang R, Dharanipragada R, Jurcak JG, Gillespy TA, Zhao Z, Musick KY, Choi YM, Barrague M, Peppard J, Smicker M, Duguid M, Parkar A, Fordham J, Kominos D Bioorg Med Chem Lett. 2012 May 1;22(9):3296-300. Epub 2012 Mar 11. PMID:22464456<ref>PMID:22464456</ref>
-The line below this paragraph, containing "STRUCTURE_3vf8", creates the "Structure Box" on the page.
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-or leave the SCENE parameter empty for the default display.
--->
-{{STRUCTURE_3vf8|  PDB=3vf8  |  SCENE=  }}
-===Crystal Structure of Spleen Tyrosine Kinase Syk Catalytic Domain with Pyrazolylbenzimidazole Inhibitor 416===
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+==See Also==
-<!--
+*[[Tyrosine kinase|Tyrosine kinase]]
-The line below this paragraph, {{ABSTRACT_PUBMED_22464456}}, adds the Publication Abstract to the page
+== References ==
-(as it appears on PubMed at http://www.pubmed.gov), where 22464456 is the PubMed ID number.
+<references/>
--->
+__TOC__
-{{ABSTRACT_PUBMED_22464456}}
+</StructureSection>
-==About this Structure==
-[[3vf8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VF8 OCA].
-==Reference==
-<ref group="xtra">PMID:022464456</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
 [[Category: Non-specific protein-tyrosine kinase]]