1xuj: Difference between revisions
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|PDB= 1xuj |SIZE=350|CAPTION= <scene name='initialview01'>1xuj</scene>, resolution 1.92Å | |PDB= 1xuj |SIZE=350|CAPTION= <scene name='initialview01'>1xuj</scene>, resolution 1.92Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand= | |LIGAND= <scene name='pdbligand=BOZ:BIS(5-AMIDINO-BENZIMIDAZOLYL)METHANONE+ZINC'>BOZ</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> | ||
|ACTIVITY= [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] | |ACTIVITY= <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> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1xuj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xuj OCA], [http://www.ebi.ac.uk/pdbsum/1xuj PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1xuj RCSB]</span> | |||
}} | }} | ||
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[[Category: Rose, M J.]] | [[Category: Rose, M J.]] | ||
[[Category: Stroud, R M.]] | [[Category: Stroud, R M.]] | ||
[[Category: complex]] | [[Category: complex]] | ||
[[Category: designed small molecule ligand with micromolar affinity]] | [[Category: designed small molecule ligand with micromolar affinity]] | ||
[[Category: trypsin-sulfate-small molecule ligand]] | [[Category: trypsin-sulfate-small molecule ligand]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:54:50 2008'' | ||
Revision as of 00:54, 31 March 2008
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| , resolution 1.92Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Activity: | Trypsin, with EC number 3.4.21.4 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
TRYPSIN-KETO-BABIM-ZN+2, PH 8.2
OverviewOverview
Many 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.
About this StructureAbout this Structure
1XUJ is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.
ReferenceReference
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
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