View source for 3rhj


==Crystal structure of the E673A mutant of the C-terminal domain of RAT 10'FORMYLTETRAHYDROFOLATE DEHYDROGENASE in complex with co-purified NADP==
<StructureSection load='3rhj' size='340' side='right'caption='[[3rhj]], [[Resolution|resolution]] 1.89&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3rhj]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RHJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RHJ 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]] 1.89&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=3rhj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rhj OCA], [https://pdbe.org/3rhj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rhj RCSB], [https://www.ebi.ac.uk/pdbsum/3rhj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rhj ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/AL1L1_RAT AL1L1_RAT] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The C-terminal domain (C(t)-FDH) of 10-formyltetrahydrofolate dehydrogenase (FDH, ALDH1L1) is an NADP(+)-dependent oxidoreductase and a structural and functional homolog of aldehyde dehydrogenases. Here we report the crystal structures of several C(t)-FDH mutants in which two essential catalytic residues adjacent to the nicotinamide ring of bound NADP(+), Cys-707 and Glu-673, were replaced separately or simultaneously. The replacement of the glutamate with an alanine causes irreversible binding of the coenzyme without any noticeable conformational changes in the vicinity of the nicotinamide ring. Additional replacement of cysteine 707 with an alanine (E673A/C707A double mutant) did not affect this irreversible binding indicating that the lack of the glutamate is solely responsible for the enhanced interaction between the enzyme and the coenzyme. The substitution of the cysteine with an alanine did not affect binding of NADP(+) but resulted in the enzyme lacking the ability to differentiate between the oxidized and reduced coenzyme: unlike the wild-type C(t)-FDH/NADPH complex, in the C707A mutant the position of NADPH is identical to the position of NADP(+) with the nicotinamide ring well ordered within the catalytic center. Thus, whereas the glutamate restricts the affinity for the coenzyme, the cysteine is the sensor of the coenzyme redox state. These conclusions were confirmed by coenzyme binding experiments. Our study further suggests that the binding of the coenzyme is additionally controlled by a long-range communication between the catalytic center and the coenzyme-binding domain and points toward an alpha-helix involved in the adenine moiety binding as a participant of this communication.

Conserved catalytic residues of the ALDH1L1 aldehyde dehydrogenase domain control binding and discharging of the coenzyme.,Tsybovsky Y, Krupenko SA J Biol Chem. 2011 Jul 1;286(26):23357-67. Epub 2011 May 3. PMID:21540484<ref>PMID:21540484</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3rhj" style="background-color:#fffaf0;"></div>

==See Also==
*[[Aldehyde dehydrogenase 3D structures|Aldehyde dehydrogenase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Tsybovsky Y]]