8wkl
From Proteopedia
(Difference between revisions)
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<table><tr><td colspan='2'>[[8wkl]] is a 8 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=8WKL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8WKL FirstGlance]. <br> | <table><tr><td colspan='2'>[[8wkl]] is a 8 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=8WKL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8WKL 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]] 2.67Å</td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.67Å</td></tr> | ||
| - | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=F66:2-(2-methyl- | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=F66:2-(2-methyl-1~{H}-indol-3-yl)ethanamine'>F66</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=8wkl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8wkl OCA], [https://pdbe.org/8wkl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8wkl RCSB], [https://www.ebi.ac.uk/pdbsum/8wkl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8wkl ProSAT]</span></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=8wkl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8wkl OCA], [https://pdbe.org/8wkl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8wkl RCSB], [https://www.ebi.ac.uk/pdbsum/8wkl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8wkl ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/STSY_RAUSE STSY_RAUSE] Catalyzes the stereospecific condensation of tryptamine with secologanin to form strictosidine, the key intermediate of indole alkaloid biosynthesis. | [https://www.uniprot.org/uniprot/STSY_RAUSE STSY_RAUSE] Catalyzes the stereospecific condensation of tryptamine with secologanin to form strictosidine, the key intermediate of indole alkaloid biosynthesis. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Besides tryptamine (1) and secologanin (2), non-cognate substrates also undergo a Pictet-Spengler reaction (PSR) catalyzed by strictosidine synthases (STR) with differing catalytic properties. We characterized the bisubstrate binding aspect of catalysis - order, affinity, and cooperativity - with STR orthologs from Rauvolfia serpentina (RsSTR) and Ophiorrhiza pumila (OpSTR) by an isothermal titration calorimetry (ITC) based 'proxy approach' that employed a non-reactive tryptamine analog (m1) to capture its inert ternary complexes with STRs and (2). ITC studies with OpSTR and (2) revealed 'tryptamine-first' cooperative binding with (1) and a simultaneous cooperative binding with (m1). Binding cooperativity among (m1) and (2) towards OpSTR was higher than RsSTR. Crystallographic study of RsSTR-(m1) complex helped to understand the unreactive binding of (m1) in terms of orientation and interactions in the RsSTR pocket. PSR with (m1) was revealed to be energetically unfeasible by the density functional theory (DFT) scans of the first hydrogen abstraction by RsSTR. The effect of pH on the bisubstrate binding to OpSTR was deciphered by molecular dynamics simulations (MDS), which also provided a molecular basis for the stability of complex of OpSTR with (m1) and (2). Therefore, we investigated STRs from a substrate binding perspective to inform drug-design and rational enzyme engineering efforts. | ||
| + | |||
| + | Proxy-approach in understanding the bisubstrate activity of strictosidine synthases.,Nitin K, Rajakumara E Int J Biol Macromol. 2024 Mar;262(Pt 2):130091. doi: , 10.1016/j.ijbiomac.2024.130091. Epub 2024 Feb 12. PMID:38354931<ref>PMID:38354931</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 8wkl" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Rauvolfia serpentina strictosidine synthase (RsSTR) in complex with a non-reactive tryptamine substitute crystallized in P1211 space group
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