View source for 3tp4


==Crystal Structure of engineered protein at the resolution 1.98A, Northeast Structural Genomics Consortium Target OR128==
<StructureSection load='3tp4' size='340' side='right'caption='[[3tp4]], [[Resolution|resolution]] 1.98&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3tp4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TP4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TP4 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.979&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3tp4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tp4 OCA], [https://pdbe.org/3tp4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tp4 RCSB], [https://www.ebi.ac.uk/pdbsum/3tp4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tp4 ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A challenge in the computational design of enzymes is that multiple properties, including substrate binding, transition state stabilization and product release, must be simultaneously optimized, and this has limited the absolute activity of successful designs. Here, we focus on a single critical property of many enzymes: the nucleophilicity of an active site residue that initiates catalysis. We design proteins with idealized serine-containing catalytic triads and assess their nucleophilicity directly in native biological systems using activity-based organophosphate probes. Crystal structures of the most successful designs show unprecedented agreement with computational models, including extensive hydrogen bonding networks between the catalytic triad (or quartet) residues, and mutagenesis experiments demonstrate that these networks are critical for serine activation and organophosphate reactivity. Following optimization by yeast display, the designs react with organophosphate probes at rates comparable to natural serine hydrolases. Co-crystal structures with diisopropyl fluorophosphate bound to the serine nucleophile suggest that the designs could provide the basis for a new class of organophosphate capture agents.

Design of activated serine-containing catalytic triads with atomic-level accuracy.,Rajagopalan S, Wang C, Yu K, Kuzin AP, Richter F, Lew S, Miklos AE, Matthews ML, Seetharaman J, Su M, Hunt JF, Cravatt BF, Baker D Nat Chem Biol. 2014 Apr 6. doi: 10.1038/nchembio.1498. PMID:24705591<ref>PMID:24705591</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3tp4" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Acton TB]]
[[Category: Baker D]]
[[Category: Everett JK]]
[[Category: Hunt JF]]
[[Category: Kuzin A]]
[[Category: Montelione GT]]
[[Category: Nair R]]
[[Category: Rajagopalan S]]
[[Category: Rost B]]
[[Category: Seetharaman J]]
[[Category: Su M]]
[[Category: Tong L]]