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==Crystal Structure of Perakine Reductase, Founder Member of a Novel AKR Subfamily with Unique Conformational Changes during NADPH Binding==
<StructureSection load='3uyi' size='340' side='right'caption='[[3uyi]], [[Resolution|resolution]] 2.31&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3uyi]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rauvolfia_serpentina Rauvolfia serpentina]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UYI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UYI 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]] 2.313&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MLZ:N-METHYL-LYSINE'>MLZ</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=3uyi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uyi OCA], [https://pdbe.org/3uyi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3uyi RCSB], [https://www.ebi.ac.uk/pdbsum/3uyi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3uyi ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PERR_RAUSE PERR_RAUSE] Aldo-keto reductase involved in the biosynthesis of monoterpenoid indole alkaloids. Broad substrate specificity enzyme with a high selectivity in the group of alkaloids. Can use perakine, 19(S),20(R)-dihydro-peraksine-17,21-al, cinnamic aldehyde, p-coumaric aldehyde and 3-(3,4,5-trimethoxyphenyl)propanal as substrates, but not ketosteroids such as progesterone. NADPH could not be replaced by NADH.<ref>PMID:18409028</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Perakine reductase (PR) catalyzes the NADPH-dependent reduction of the aldehyde perakine to yield the alcohol raucaffrinoline in the biosynthetic pathway of ajmaline in Rauvolfia, a key step in indole alkaloid biosynthesis. Sequence alignment shows that PR is the founder of the new AKR13D subfamily and is designated AKR13D1. The x-ray structure of methylated His(6)-PR was solved to 2.31 A. However, the active site of PR was blocked by the connected parts of the neighbor symmetric molecule in the crystal. To break the interactions and obtain the enzyme-ligand complexes, the A213W mutant was generated. The atomic structure of His(6)-PR-A213W complex with NADPH was determined at 1.77 A. Overall, PR folds in an unusual alpha(8)/beta(6) barrel that has not been observed in any other AKR protein to date. NADPH binds in an extended pocket, but the nicotinamide riboside moiety is disordered. Upon NADPH binding, dramatic conformational changes and movements were observed: two additional beta-strands in the C terminus become ordered to form one alpha-helix, and a movement of up to 24 A occurs. This conformational change creates a large space that allows the binding of substrates of variable size for PR and enhances the enzyme activity; as a result cooperative kinetics are observed as NADPH is varied. As the founding member of the new AKR13D subfamily, PR also provides a structural template and model of cofactor binding for the AKR13 family.

Crystal structure of perakine reductase, founding member of a novel aldo-keto reductase (AKR) subfamily that undergoes unique conformational changes during NADPH binding.,Sun L, Chen Y, Rajendran C, Mueller U, Panjikar S, Wang M, Mindnich R, Rosenthal C, Penning TM, Stockigt J J Biol Chem. 2012 Mar 30;287(14):11213-21. Epub 2012 Feb 13. PMID:22334702<ref>PMID:22334702</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3uyi" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Rauvolfia serpentina]]
[[Category: Chen Y]]
[[Category: Mindnich R]]
[[Category: Mueller U]]
[[Category: Panjikar S]]
[[Category: Penning TM]]
[[Category: Rajendran C]]
[[Category: Rosenthal C]]
[[Category: Stoeckigt J]]
[[Category: Sun L]]
[[Category: Wang M]]