View source for 8dkq


==Minimal PutA proline dehydrogenase domain (design #2) complexed with 2-(Furan-2-yl)acetic acid==
<StructureSection load='8dkq' size='340' side='right'caption='[[8dkq]], [[Resolution|resolution]] 1.72&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8dkq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Sinorhizobium_meliloti_SM11 Sinorhizobium meliloti SM11]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DKQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DKQ 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]] 1.72&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SJU:(furan-2-yl)acetic+acid'>SJU</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=8dkq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dkq OCA], [https://pdbe.org/8dkq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dkq RCSB], [https://www.ebi.ac.uk/pdbsum/8dkq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dkq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/F7X6I3_SINMM F7X6I3_SINMM] Oxidizes proline to glutamate for use as a carbon and nitrogen source.[PIRNR:PIRNR000197]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Proline dehydrogenase (PRODH) catalyzes the FAD-dependent oxidation of l-proline to Delta1-pyrroline-5-carboxylate and is a target for inhibitor discovery because of its importance in cancer cell metabolism. Because human PRODH is challenging to purify, the PRODH domains of the bacterial bifunctional enzyme proline utilization A (PutA) have been used for inhibitor development. These systems have limitations due to large polypeptide chain length, conformational flexibility and the presence of domains unrelated to PRODH activity. Herein, we report the engineering of minimal PRODH domains for inhibitor discovery. The best designs contain one-third of the 1233-residue PutA from Sinorhizobium meliloti and include a linker that replaces the PutA alpha-domain. The minimal PRODHs exhibit near wild-type enzymatic activity and are susceptible to known inhibitors and inactivators. Crystal structures of minimal PRODHs inhibited by S-(-)-tetrahydro-2-furoic acid and 2-(furan-2-yl)acetic acid were determined at 1.23 and 1.72 A resolution. Minimal PRODHs should be useful in chemical probe discovery.

Structure-based engineering of minimal proline dehydrogenase domains for inhibitor discovery.,Bogner AN, Ji J, Tanner JJ Protein Eng Des Sel. 2022 Feb 17;35:gzac016. doi: 10.1093/protein/gzac016. PMID:36448708<ref>PMID:36448708</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8dkq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Sinorhizobium meliloti SM11]]
[[Category: Bogner AN]]
[[Category: Tanner JJ]]