1jh1

<table><tr><td colspan='2'>[[1jh1]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JH1 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1JH1 FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=JST:BUT-3-ENYL-[5-(4-CHLORO-PHENYL)-3,6-DIHYDRO-[1,3,4]THIADIAZIN-2-YLIDENE]-AMINE'>JST</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>

<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Neutrophil_collagenase Neutrophil collagenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.34 3.4.24.34] </span></td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1jh1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jh1 OCA], [http://pdbe.org/1jh1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1jh1 RCSB], [http://www.ebi.ac.uk/pdbsum/1jh1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1jh1 ProSAT]</span></td></tr>

[[http://www.uniprot.org/uniprot/MMP8_HUMAN MMP8_HUMAN]] Can degrade fibrillar type I, II, and III collagens.

<div style="background-color:#fffaf0;">

== Publication Abstract from PubMed ==

We describe a new generation of heterocyclic nonpeptide matrix metalloproteinase (MMP) inhibitors derived from a 6H-1,3,4-thiadiazine scaffold. A screening effort was utilized to identify some chiral 6-methyl-1,3,4-thiadiazines that are weak inhibitors of the catalytic domain of human neutrophil collagenase (cdMMP-8). Further optimization of the lead compounds revealed general design principles that involve the placement of a phenyl or thienyl group at position 5 of the thiadiazine ring, to improve unprimed side affinity; the incorporation of an amino group at position 2 of the thiadiazine ring as the chelating agent for the catalytic zinc; the placement of a N-sulfonamide-substituted amino acid residue at the amino group, to improve primed side affinity; and the attachment of diverse functional groups at position 4 or 5 of the phenyl or thienyl group at the unprimed side, to improve selectivity. The new compounds were assayed against eight different matrix metalloproteinases, MMP-1, cdMMP-2, cdMMP-8, MMP-9, cdMMP-12, cdMMP-13, cdMMP-14, and the ectodomain of MMP-14, respectively. A unique combination of the above-described modifications produced the selective inhibitor (2R)-N-[5-(4-bromophenyl)-6H-1,3,4-thiadiazin-2-yl]-2-[(phenylsulfonyl)ami no]propanamide with high affinity for MMP-9 (K(i) = 40 nM). X-ray crystallographic data obtained for cdMMP-8 cocrystallized with N-allyl-5-(4-chlorophenyl)-6H-1,3,4-thiadiazin-2-amine hydrobromide gave detailed design information on binding interactions for thiadiazine-based MMP inhibitors.

Structure-based design and synthesis of potent matrix metalloproteinase inhibitors derived from a 6H-1,3,4-thiadiazine scaffold.,Schroder J, Henke A, Wenzel H, Brandstetter H, Stammler HG, Stammler A, Pfeiffer WD, Tschesche H J Med Chem. 2001 Sep 27;44(20):3231-43. PMID:11563922<ref>PMID:11563922</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

</div>

<div class="pdbe-citations 1jh1" style="background-color:#fffaf0;"></div>

== References ==

<references/>

[[Category: Human]]

[[Category: Brandstetter, H]]

[[Category: Henke, A]]

[[Category: Pfeiffer, W D]]

[[Category: Schroder, J]]

[[Category: Stammler, A]]

[[Category: Stammler, H G]]

[[Category: Tschesche, H]]

[[Category: Wenzel, H]]

[[Category: Thiadiazine]]