4mrd: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Crystal structure of the murine cd44 hyaluronan binding domain complex with a small molecule== | |||
<StructureSection load='4mrd' size='340' side='right' caption='[[4mrd]], [[Resolution|resolution]] 2.55Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4mrd]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MRD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MRD FirstGlance]. <br> | |||
==Function== | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=BDP:BETA-D-GLUCOPYRANURONIC+ACID'>BDP</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4mre|4mre]], [[4mrf|4mrf]], [[4mrg|4mrg]], [[4mrh|4mrh]], [[4np3|4np3]], [[4np2|4np2]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Cd44, Cd44 Ly-24, Ly-24 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4mrd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mrd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4mrd RCSB], [http://www.ebi.ac.uk/pdbsum/4mrd PDBsum]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/CD44_MOUSE CD44_MOUSE]] Main cell surface receptor for hyaluronate. Adhesion to mucosal high endothelial venule and to types I and VI collagen. Probably involved in matrix adhesion, lymphocyte activation and lymph node homing. | [[http://www.uniprot.org/uniprot/CD44_MOUSE CD44_MOUSE]] Main cell surface receptor for hyaluronate. Adhesion to mucosal high endothelial venule and to types I and VI collagen. Probably involved in matrix adhesion, lymphocyte activation and lymph node homing. | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Selective inhibitors of hyaluronan (HA) binding to the cell surface receptor CD44 will have value as probes of CD44-mediated signaling and have potential as therapeutic agents in chronic inflammation, cardiovascular disease, and cancer. Using biophysical binding assays, fragment screening, and crystallographic characterization of complexes with the CD44 HA binding domain, we have discovered an inducible pocket adjacent to the HA binding groove into which small molecules may bind. Iterations of fragment combination and structure-driven design have allowed identification of a series of 1,2,3,4-tetrahydroisoquinolines as the first nonglycosidic inhibitors of the CD44-HA interaction. The affinity of these molecules for the CD44 HA binding domain parallels their ability to interfere with CD44 binding to polymeric HA in vitro. X-ray crystallographic complexes of lead compounds are described and compared to a new complex with a short HA tetrasaccharide, to establish the tetrahydroisoquinoline pharmacophore as an attractive starting point for lead optimization. | |||
Fragment-Based Identification of an Inducible Binding Site on Cell Surface Receptor CD44 for the Design of Protein-Carbohydrate Interaction Inhibitors.,Liu LK, Finzel BC J Med Chem. 2014 Mar 27;57(6):2714-25. doi: 10.1021/jm5000276. Epub 2014 Mar 7. PMID:24606063<ref>PMID:24606063</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
[[Category: Finzel, B | == References == | ||
[[Category: Liu, L K | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Lk3 transgenic mice]] | |||
[[Category: Finzel, B]] | |||
[[Category: Liu, L K]] | |||
[[Category: Cell adhesion]] | [[Category: Cell adhesion]] | ||
[[Category: Cell receptor]] | [[Category: Cell receptor]] | ||
Revision as of 00:07, 26 December 2014
Crystal structure of the murine cd44 hyaluronan binding domain complex with a small moleculeCrystal structure of the murine cd44 hyaluronan binding domain complex with a small molecule
Structural highlights
Function[CD44_MOUSE] Main cell surface receptor for hyaluronate. Adhesion to mucosal high endothelial venule and to types I and VI collagen. Probably involved in matrix adhesion, lymphocyte activation and lymph node homing. Publication Abstract from PubMedSelective inhibitors of hyaluronan (HA) binding to the cell surface receptor CD44 will have value as probes of CD44-mediated signaling and have potential as therapeutic agents in chronic inflammation, cardiovascular disease, and cancer. Using biophysical binding assays, fragment screening, and crystallographic characterization of complexes with the CD44 HA binding domain, we have discovered an inducible pocket adjacent to the HA binding groove into which small molecules may bind. Iterations of fragment combination and structure-driven design have allowed identification of a series of 1,2,3,4-tetrahydroisoquinolines as the first nonglycosidic inhibitors of the CD44-HA interaction. The affinity of these molecules for the CD44 HA binding domain parallels their ability to interfere with CD44 binding to polymeric HA in vitro. X-ray crystallographic complexes of lead compounds are described and compared to a new complex with a short HA tetrasaccharide, to establish the tetrahydroisoquinoline pharmacophore as an attractive starting point for lead optimization. Fragment-Based Identification of an Inducible Binding Site on Cell Surface Receptor CD44 for the Design of Protein-Carbohydrate Interaction Inhibitors.,Liu LK, Finzel BC J Med Chem. 2014 Mar 27;57(6):2714-25. doi: 10.1021/jm5000276. Epub 2014 Mar 7. PMID:24606063[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||||