5f03

<StructureSection load='5f03' size='340' side='right' caption='[[5f03]], [[Resolution|resolution]] 1.94&Aring;' scene=''>

<table><tr><td colspan='2'>[[5f03]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F03 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5F03 FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5TA:(5~{S})-5-[[3-(AMINOMETHYL)PHENOXY]METHYL]-3-[3-[2-(2-CHLORANYLPYRIDIN-3-YL)ETHYNYL]PHENYL]-1,3-OXAZOLIDIN-2-ONE'>5TA</scene></td></tr>

<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Tryptase Tryptase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.59 3.4.21.59] </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=5f03 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f03 OCA], [http://pdbe.org/5f03 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5f03 RCSB], [http://www.ebi.ac.uk/pdbsum/5f03 PDBsum]</span></td></tr>

[[http://www.uniprot.org/uniprot/TRYB1_HUMAN TRYB1_HUMAN]] Tryptase is the major neutral protease present in mast cells and is secreted upon the coupled activation-degranulation response of this cell type (By similarity).

We present a series of small molecule drug discovery case studies where computational methods were prospectively employed to impact Roche research projects, with the aim of highlighting those methods that provide real added value. Our brief accounts encompass a broad range of methods and techniques applied to a variety of enzymes and receptors. Most of these are based on judicious application of knowledge about molecular conformations and interactions: filling of lipophilic pockets to gain affinity or selectivity, addition of polar substituents, scaffold hopping, transfer of SAR, conformation analysis, and molecular overlays. A case study of sequence-driven focused screening is presented to illustrate how appropriate preprocessing of information enables effective exploitation of prior knowledge. We conclude that qualitative statements enabling chemists to focus on promising regions of chemical space are often more impactful than quantitative prediction.

 

== References ==

[[Category: Tryptase]]

[[Category: Banner, D]]

[[Category: Benz, J]]

[[Category: Joseph, C]]

[[Category: Kuglstatter, A]]

[[Category: Serine proteinase]]