6tcx: Difference between revisions
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<StructureSection load='6tcx' size='340' side='right'caption='[[6tcx]], [[Resolution|resolution]] 1.65Å' scene=''> | <StructureSection load='6tcx' size='340' side='right'caption='[[6tcx]], [[Resolution|resolution]] 1.65Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6tcx]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6tcx]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Carica_papaya Carica papaya]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TCX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TCX FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=N1W:(2~{R})-2-[[(1~{S})-1-[(6~{S})-2-azanyl-1,4,5,6-tetrahydropyrimidin-6-yl]-2-[[(2~{S})-3-methyl-1-oxidanylidene-1-[[(2~{S})-1-oxidanyl-3-phenyl-propan-2-yl]amino]butan-2-yl]amino]-2-oxidanylidene-ethyl]carbamoylamino]-3-(4-hydroxyphenyl)propanoic+acid'>N1W</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.65Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=N1W:(2~{R})-2-[[(1~{S})-1-[(6~{S})-2-azanyl-1,4,5,6-tetrahydropyrimidin-6-yl]-2-[[(2~{S})-3-methyl-1-oxidanylidene-1-[[(2~{S})-1-oxidanyl-3-phenyl-propan-2-yl]amino]butan-2-yl]amino]-2-oxidanylidene-ethyl]carbamoylamino]-3-(4-hydroxyphenyl)propanoic+acid'>N1W</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6tcx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tcx OCA], [https://pdbe.org/6tcx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tcx RCSB], [https://www.ebi.ac.uk/pdbsum/6tcx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tcx ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/PAPA1_CARPA PAPA1_CARPA] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Streptomyces mobaraensis produces the papain inhibitor SPI consisting of a 12 kDa protein and small active compounds (SPI(ac)). Purification of the papain inhibitory compounds resulted in four diverse chymostatin derivatives that were characterized by NMR and MS analysis. Chymostatins are hydrophobic tetrapeptide aldehydes from streptomycetes, e.g., S. lavendulae and S. hygroscopicus, that reverse chymosin-mediated angiotensin activation and inhibit other serine and cysteine proteases. Chymotrypsin and papain were both inhibited by the SPI(ac) compounds in the low nanomolar range. SPI(ac) differs from the characterized chymostatins by the exchange of phenylalanine for tyrosine. The crystal structure of one of these chymostatin variants confirmed its molecular structure and revealed a S-configured hemithioacetal bond with the catalytic Cys25 thiolate as well as close interactions with hydrophobic S1 and S2 subsite amino acids. A model for chymostatin biosynthesis is provided based on the discovery of clustered genes encoding several putative nonribosomal peptide synthetases; among them, there is the unusual CstF enzyme that accommodates two canonical amino acid activation domains as well as three peptide carrier protein domains. | |||
Decoding the Papain Inhibitor from Streptomyces mobaraensis as Being Hydroxylated Chymostatin Derivatives: Purification, Structure Analysis, and Putative Biosynthetic Pathway.,Juettner NE, Bogen JP, Bauer TA, Knapp S, Pfeifer F, Huettenhain SH, Meusinger R, Kraemer A, Fuchsbauer HL J Nat Prod. 2020 Oct 23;83(10):2983-2995. doi: 10.1021/acs.jnatprod.0c00201. Epub , 2020 Sep 30. PMID:32998509<ref>PMID:32998509</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6tcx" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Papain|Papain]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Carica papaya]] | [[Category: Carica papaya]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Arrowsmith CH]] | |||
[[Category: Arrowsmith | [[Category: Bountra C]] | ||
[[Category: Bountra | [[Category: Edwards AM]] | ||
[[Category: Edwards | [[Category: Fuchsbauer H-L]] | ||
[[Category: Fuchsbauer | [[Category: Juettner NE]] | ||
[[Category: Juettner | [[Category: Knapp S]] | ||
[[Category: Knapp | [[Category: Kraemer A]] | ||
[[Category: Kraemer | |||
Latest revision as of 15:59, 24 January 2024
Papain bound to a natural cysteine protease inhibitor from Streptomyces mobaraensisPapain bound to a natural cysteine protease inhibitor from Streptomyces mobaraensis
Structural highlights
FunctionPublication Abstract from PubMedStreptomyces mobaraensis produces the papain inhibitor SPI consisting of a 12 kDa protein and small active compounds (SPI(ac)). Purification of the papain inhibitory compounds resulted in four diverse chymostatin derivatives that were characterized by NMR and MS analysis. Chymostatins are hydrophobic tetrapeptide aldehydes from streptomycetes, e.g., S. lavendulae and S. hygroscopicus, that reverse chymosin-mediated angiotensin activation and inhibit other serine and cysteine proteases. Chymotrypsin and papain were both inhibited by the SPI(ac) compounds in the low nanomolar range. SPI(ac) differs from the characterized chymostatins by the exchange of phenylalanine for tyrosine. The crystal structure of one of these chymostatin variants confirmed its molecular structure and revealed a S-configured hemithioacetal bond with the catalytic Cys25 thiolate as well as close interactions with hydrophobic S1 and S2 subsite amino acids. A model for chymostatin biosynthesis is provided based on the discovery of clustered genes encoding several putative nonribosomal peptide synthetases; among them, there is the unusual CstF enzyme that accommodates two canonical amino acid activation domains as well as three peptide carrier protein domains. Decoding the Papain Inhibitor from Streptomyces mobaraensis as Being Hydroxylated Chymostatin Derivatives: Purification, Structure Analysis, and Putative Biosynthetic Pathway.,Juettner NE, Bogen JP, Bauer TA, Knapp S, Pfeifer F, Huettenhain SH, Meusinger R, Kraemer A, Fuchsbauer HL J Nat Prod. 2020 Oct 23;83(10):2983-2995. doi: 10.1021/acs.jnatprod.0c00201. Epub , 2020 Sep 30. PMID:32998509[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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