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==Crystal structure of NzeB in complex with cyclo-(L-Trp-L-Pro)== | ==Crystal structure of NzeB in complex with cyclo-(L-Trp-L-Pro)== | ||
<StructureSection load='6xai' size='340' side='right'caption='[[6xai]]' scene=''> | <StructureSection load='6xai' size='340' side='right'caption='[[6xai]], [[Resolution|resolution]] 1.49Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XAI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XAI FirstGlance]. <br> | <table><tr><td colspan='2'>[[6xai]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_sp._nrrl_f-5053 Streptomyces sp. nrrl f-5053]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XAI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XAI FirstGlance]. <br> | ||
</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=6xai FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xai OCA], [https://pdbe.org/6xai PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xai RCSB], [https://www.ebi.ac.uk/pdbsum/6xai PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xai ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=QRP:(3S,8AS)-3-(1H-INDOL-3-YLMETHYL)HEXAHYDROPYRROLO[1,2-A]PYRAZINE-1,4-DIONE'>QRP</scene></td></tr> | ||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</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=6xai FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xai OCA], [https://pdbe.org/6xai PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xai RCSB], [https://www.ebi.ac.uk/pdbsum/6xai PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xai ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The dimeric diketopiperazine (DKPs) alkaloids are a diverse family of natural products (NPs) whose unique structural architectures and biological activities have inspired the development of new synthetic methodologies to access these molecules. However, catalyst-controlled methods that enable the selective formation of constitutional and stereoisomeric dimers from a single monomer are lacking. To resolve this long-standing synthetic challenge, we sought to characterize the biosynthetic enzymes that assemble these NPs for application in biocatalytic syntheses. Genome mining enabled identification of the cytochrome P450, NzeB (Streptomyces sp. NRRL F-5053), which catalyzes both intermolecular carbon-carbon (C-C) and carbon-nitrogen (C-N) bond formation. To identify the molecular basis for the flexible site-selectivity, stereoselectivity, and chemoselectivity of NzeB, we obtained high-resolution crystal structures (1.5 A) of the protein in complex with native and non-native substrates. This, to our knowledge, represents the first crystal structure of an oxidase catalyzing direct, intermolecular C-H amination. Site-directed mutagenesis was utilized to assess the role individual active-site residues play in guiding selective DKP dimerization. Finally, computational approaches were employed to evaluate plausible mechanisms regarding NzeB function and its ability to catalyze both C-C and C-N bond formation. These results provide a structural and computational rationale for the catalytic versatility of NzeB, as well as new insights into variables that control selectivity of CYP450 diketopiperazine dimerases. | |||
Structure and Function of NzeB, a Versatile C-C and C-N Bond-Forming Diketopiperazine Dimerase.,Shende VV, Khatri Y, Newmister SA, Sanders JN, Lindovska P, Yu F, Doyon TJ, Kim J, Houk KN, Movassaghi M, Sherman DH J Am Chem Soc. 2020 Oct 14;142(41):17413-17424. doi: 10.1021/jacs.0c06312. Epub, 2020 Sep 30. PMID:32786740<ref>PMID:32786740</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6xai" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Doyon | [[Category: Streptomyces sp. nrrl f-5053]] | ||
[[Category: Houk | [[Category: Doyon, T J]] | ||
[[Category: Khatri Y]] | [[Category: Houk, K N]] | ||
[[Category: Kim J]] | [[Category: Khatri, Y]] | ||
[[Category: Lindovska P]] | [[Category: Kim, J]] | ||
[[Category: Movassaghi M]] | [[Category: Lindovska, P]] | ||
[[Category: Newmister | [[Category: Movassaghi, M]] | ||
[[Category: Sanders | [[Category: Newmister, S A]] | ||
[[Category: Shende | [[Category: Sanders, J N]] | ||
[[Category: Sherman | [[Category: Shende, V V]] | ||
[[Category: Yu F]] | [[Category: Sherman, D H]] | ||
[[Category: Yu, F]] | |||
[[Category: Dimerase]] | |||
[[Category: Monooxygenase]] | |||
[[Category: Oxidoreductase]] | |||
[[Category: P450]] | |||