View source for 4bi9


==Crystal structure of wild-type SCP2 thiolase from Trypanosoma brucei.==
<StructureSection load='4bi9' size='340' side='right'caption='[[4bi9]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4bi9]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei_brucei_TREU927 Trypanosoma brucei brucei TREU927]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BI9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BI9 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]] 2.45&#8491;</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=4bi9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bi9 OCA], [https://pdbe.org/4bi9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bi9 RCSB], [https://www.ebi.ac.uk/pdbsum/4bi9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bi9 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q57XD5_TRYB2 Q57XD5_TRYB2] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Thiolases are essential CoA dependent enzymes in lipid metabolism. Here we report on crystal structures of trypanosomal and leishmanial SCP2-thiolases. Trypanosomatidae cause various widespread, devastating (sub)-tropical diseases, for which adequate treatment is lacking. The structures reveal the unique geometry of the active site of this poorly characterized subfamily of thiolases. The key catalytic residues of the classical thiolases are two cysteines, functioning as a nucleophile and an acid/base, respectively. The latter cysteine is part of a CxG-motif. Interestingly, this cysteine is not conserved in SCP2-thiolases. The structural comparisons now show that in SCP2-thiolases the catalytic acid/base is provided by the cysteine of the HDCF-motif, which is unique for this thiolase subfamily. This HDCF-cysteine is spatially equivalent to the CxG-cysteine of classical thiolases. The HDCF-cysteine is activated for acid/base catalysis by two main chain NH-atoms, instead of two waters, as present in the CxG-active site. The structural results have been complemented with enzyme activity data, confirming the importance of the HDCF-cysteine for catalysis. The data obtained suggest that these trypanosomatid SCP2-thiolases are biosynthetic thiolases. These findings provide promise for drug discovery as biosynthetic thiolases catalyse the first step of the sterol biosynthesis pathway that is essential in several of these parasites.

Crystal structures of SCP2-thiolases of Trypanosomatidae, human pathogens causing widespread tropical diseases: the importance for catalysis of the cysteine of the unique HDCF loop.,Harijan RK, Kiema TR, Karjalainen MP, Janardan N, Murthy MR, Weiss MS, Michels PA, Wierenga RK Biochem J. 2013 Aug 2. PMID:23909465<ref>PMID:23909465</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4bi9" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Trypanosoma brucei brucei TREU927]]
[[Category: Harijan RK]]
[[Category: Kiema T-R]]
[[Category: Michels PAM]]
[[Category: Weiss MS]]
[[Category: Wierenga RK]]