1c2d: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==RECRUITING ZINC TO MEDIATE POTENT, SPECIFIC INHIBITION OF SERINE PROTEASES== | ==RECRUITING ZINC TO MEDIATE POTENT, SPECIFIC INHIBITION OF SERINE PROTEASES== | ||
<StructureSection load='1c2d' size='340' side='right' caption='[[1c2d]], [[Resolution|resolution]] 1.65Å' scene=''> | <StructureSection load='1c2d' size='340' side='right' caption='[[1c2d]], [[Resolution|resolution]] 1.65Å' scene=''> | ||
| Line 6: | Line 7: | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1c2e|1c2e]], [[1c2f|1c2f]], [[1c2g|1c2g]], [[1c2h|1c2h]], [[1c2i|1c2i]], [[1c2l|1c2l]], [[1c2m|1c2m]], [[1c1n|1c1n]], [[1c1o|1c1o]], [[1c1p|1c1p]], [[1c1q|1c1q]], [[1c1r|1c1r]], [[1c1s|1c1s]], [[1c1t|1c1t]], [[1c1u|1c1u]], [[1c1v|1c1v]], [[1c1w|1c1w]], [[1c2j|1c2j]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1c2e|1c2e]], [[1c2f|1c2f]], [[1c2g|1c2g]], [[1c2h|1c2h]], [[1c2i|1c2i]], [[1c2l|1c2l]], [[1c2m|1c2m]], [[1c1n|1c1n]], [[1c1o|1c1o]], [[1c1p|1c1p]], [[1c1q|1c1q]], [[1c1r|1c1r]], [[1c1s|1c1s]], [[1c1t|1c1t]], [[1c1u|1c1u]], [[1c1v|1c1v]], [[1c1w|1c1w]], [[1c2j|1c2j]]</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Trypsin Trypsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.4 3.4.21.4] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Trypsin Trypsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.4 3.4.21.4] </span></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=1c2d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c2d OCA], [http://pdbe.org/1c2d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1c2d RCSB], [http://www.ebi.ac.uk/pdbsum/1c2d PDBsum]</span></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=1c2d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c2d OCA], [http://pdbe.org/1c2d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1c2d RCSB], [http://www.ebi.ac.uk/pdbsum/1c2d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1c2d ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
| Line 27: | Line 28: | ||
</div> | </div> | ||
<div class="pdbe-citations 1c2d" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 1c2d" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 11:07, 29 November 2017
RECRUITING ZINC TO MEDIATE POTENT, SPECIFIC INHIBITION OF SERINE PROTEASESRECRUITING ZINC TO MEDIATE POTENT, SPECIFIC INHIBITION OF SERINE PROTEASES
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedMany serine proteases are targets for therapeutic intervention because they often play key roles in disease. Small molecule inhibitors of serine proteases with high affinity are especially interesting as they could be used as scaffolds from which to develop drugs selective for protease targets. One such inhibitor is bis(5-amidino-2-benzimidazolyl)methane (BABIM), standing out as the best inhibitor of trypsin (by a factor of over 100) in a series of over 60 relatively closely related analogues. By probing the structural basis of inhibition, we discovered, using crystallographic methods, a new mode of high-affinity binding in which a Zn2+ ion is tetrahedrally coordinated between two chelating nitrogens of BABIM and two active site residues, His57 and Ser 195. Zn2+, at subphysiological levels, enhances inhibition by over 10(3)-fold. The distinct Zn2+ coordination geometry implies a strong dependence of affinity on substituents. This unique structural paradigm has enabled development of potent, highly selective, Zn2+-dependent inhibitors of several therapeutically important serine proteases, using a physiologically ubiquitous metal ion. Design of potent selective zinc-mediated serine protease inhibitors.,Katz BA, Clark JM, Finer-Moore JS, Jenkins TE, Johnson CR, Ross MJ, Luong C, Moore WR, Stroud RM Nature. 1998 Feb 5;391(6667):608-12. PMID:9468142[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||||