View source for 8rkr


==Structure of human DELTA-1-PYRROLINE-5-CARBOXYLATE DEHYDROGENASE (ALDH4A1) complexed with a monophosphate-tweezer==
<StructureSection load='8rkr' size='340' side='right'caption='[[8rkr]], [[Resolution|resolution]] 1.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8rkr]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8RKR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8RKR 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]] 1.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1H1O:(1R,5S,9S,16R,20R,24S,28S,35R)-22-(Dihydroxyphosphoryloxy)tridecacyclo[22.14.1.15,20.19,16.128,35.02,23.04,21.06,19.08,17.010,15.025,38.027,36.029,34]dotetraconta-2(23),3,6,8(17),10,12,14,18,21,25,27(36),29,31,33,37-pentadecaen-3-ol'>A1H1O</scene>, <scene name='pdbligand=BEZ:BENZOIC+ACID'>BEZ</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=8rkr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8rkr OCA], [https://pdbe.org/8rkr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8rkr RCSB], [https://www.ebi.ac.uk/pdbsum/8rkr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8rkr ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/AL4A1_HUMAN AL4A1_HUMAN] Hyperprolinemia type 2. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/AL4A1_HUMAN AL4A1_HUMAN] Irreversible conversion of delta-1-pyrroline-5-carboxylate (P5C), derived either from proline or ornithine, to glutamate. This is a necessary step in the pathway interconnecting the urea and tricarboxylic acid cycles. The preferred substrate is glutamic gamma-semialdehyde, other substrates include succinic, glutaric and adipic semialdehydes.<ref>PMID:22516612</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
To understand the biological relevance and mode of action of artificial protein ligands, crystal structures with their protein targets are essential. Here, we describe and investigate all known crystal structures that contain a so-called "molecular tweezer" or one of its derivatives with an attached natural ligand on the respective target protein. The aromatic ring system of these compounds is able to include lysine and arginine side chains, supported by one or two phosphate groups that are attached to the half-moon-shaped molecule. Due to their marked preference for basic amino acids and the fully reversible binding mode, molecular tweezers are able to counteract pathologic protein aggregation and are currently being developed as disease-modifying therapies against neurodegenerative diseases such as Alzheimer's and Parkinson's disease. We analyzed the corresponding crystal structures with 14-3-3 proteins in complex with mono- and diphosphate tweezers. Furthermore, we solved crystal structures of two different tweezer variants in complex with the enzyme Delta(1)-Pyrroline-5-carboxyl-dehydrogenase (P5CDH) and found that the tweezers are bound to a lysine and methionine side chain, respectively. The different binding modes and their implications for affinity and specificity are discussed, as well as the general problems in crystallizing protein complexes with artificial ligands.

How Do Molecular Tweezers Bind to Proteins? Lessons from X-ray Crystallography.,Porfetye AT, Stege P, Rebollido-Rios R, Hoffmann D, Schrader T, Vetter IR Molecules. 2024 Apr 12;29(8):1764. doi: 10.3390/molecules29081764. PMID:38675584<ref>PMID:38675584</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8rkr" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Porfetye AT]]
[[Category: Vetter IR]]