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7lhc

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NMR Solution Structure of [T20K]kalata B1

Structural highlights

7lhc is a 1 chain structure with sequence from Oldenlandia affinis. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

KAB1_OLDAF Probably participates in a plant defense mechanism. Has antibiotic activity. Has a diuretic effect. Has a uterotonic effect in humans. Active against the Gram-positive S.aureus with a minimum inhibition concentration of approximately 0.2 microM. Relatively ineffective against Gram-negative bacteria such as E.coli and P.aeruginosa. Inhibitory effect on the growth and development of larvae from H.punctigera. The unmodified form has hemolytic activity, the oxidized form lacks hemolytic activity. If the protein is linearized, hemolytic activity is lost.^[1] ^[2]

Publication Abstract from PubMed

The cyclotide T20K inhibits the proliferation of human immune cells and is currently in clinical trials for multiple sclerosis. Here, we provide novel functional data and mechanistic insights into structure-activity relationships of T20K. Analogs with partial or complete reduction of the cystine knot had loss of function in proliferation experiments. Similarly, an acyclic analog of T20K was inactive in lymphocyte bioassays. The lack of activity of non-native peptide analogs appears to be associated with the ability of cyclotides to interact with and penetrate cell membranes, since cellular uptake studies demonstrated fast fractional transfer only of the native peptide into the cytosol of human immune cells. Therefore, structural differences between cyclic and linear native folded peptides were investigated by NMR to elucidate structure-activity relationships. Acyclic T20K had a less rigid backbone and considerable structural changes in loops 1 and 6 compared to the native cyclic T20K, supporting the idea that the cyclic cystine knot motif is a unique bioactive scaffold. This study provides evidence that this structural motif in cyclotides governs bioactivity, interactions with and transport across biological membranes, and the structural integrity of these peptides. These observations could be useful to understand the structure-activity of other cystine knot proteins due to the structural conservation of the cystine knot motif across evolution and to provide guidance for the design of novel cyclic cysteine-stabilized molecules.

Importance of the Cyclic Cystine Knot Structural Motif for Immunosuppressive Effects of Cyclotides.,Hellinger R, Muratspahic E, Devi S, Koehbach J, Vasileva M, Harvey PJ, Craik DJ, Grundemann C, Gruber CW ACS Chem Biol. 2021 Sep 30. doi: 10.1021/acschembio.1c00524. PMID:34592097^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Plan MR, Goransson U, Clark RJ, Daly NL, Colgrave ML, Craik DJ. The cyclotide fingerprint in oldenlandia affinis: elucidation of chemically modified, linear and novel macrocyclic peptides. Chembiochem. 2007 Jun 18;8(9):1001-11. PMID:17534989 doi:http://dx.doi.org/10.1002/cbic.200700097
↑ Barry DG, Daly NL, Clark RJ, Sando L, Craik DJ. Linearization of a naturally occurring circular protein maintains structure but eliminates hemolytic activity. Biochemistry. 2003 Jun 10;42(22):6688-95. PMID:12779323 doi:http://dx.doi.org/10.1021/bi027323n
↑ Hellinger R, Muratspahic E, Devi S, Koehbach J, Vasileva M, Harvey PJ, Craik DJ, Grundemann C, Gruber CW. Importance of the Cyclic Cystine Knot Structural Motif for Immunosuppressive Effects of Cyclotides. ACS Chem Biol. 2021 Sep 30. doi: 10.1021/acschembio.1c00524. PMID:34592097 doi:http://dx.doi.org/10.1021/acschembio.1c00524

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7lhc"

Categories: Large Structures | Oldenlandia affinis | Craik DJ | Gruber CW | Harvey PJ

@@ Line 1: / Line 1: @@
 ==NMR Solution Structure of [T20K]kalata B1==
-<StructureSection load='7lhc' size='340' side='right'caption='[[7lhc]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='7lhc' size='340' side='right'caption='[[7lhc]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7lhc]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LHC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LHC FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7lhc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Oldenlandia_affinis Oldenlandia affinis]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LHC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LHC 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=7lhc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lhc OCA], [https://pdbe.org/7lhc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lhc RCSB], [https://www.ebi.ac.uk/pdbsum/7lhc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lhc ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/KAB1_OLDAF KAB1_OLDAF]] Probably participates in a plant defense mechanism. Has antibiotic activity. Has a diuretic effect. Has a uterotonic effect in humans. Active against the Gram-positive S.aureus with a minimum inhibition concentration of approximately 0.2 microM. Relatively ineffective against Gram-negative bacteria such as E.coli and P.aeruginosa. Inhibitory effect on the growth and development of larvae from H.punctigera. The unmodified form has hemolytic activity, the oxidized form lacks hemolytic activity. If the protein is linearized, hemolytic activity is lost.<ref>PMID:17534989</ref> <ref>PMID:12779323</ref>
+[https://www.uniprot.org/uniprot/KAB1_OLDAF KAB1_OLDAF] Probably participates in a plant defense mechanism. Has antibiotic activity. Has a diuretic effect. Has a uterotonic effect in humans. Active against the Gram-positive S.aureus with a minimum inhibition concentration of approximately 0.2 microM. Relatively ineffective against Gram-negative bacteria such as E.coli and P.aeruginosa. Inhibitory effect on the growth and development of larvae from H.punctigera. The unmodified form has hemolytic activity, the oxidized form lacks hemolytic activity. If the protein is linearized, hemolytic activity is lost.<ref>PMID:17534989</ref> <ref>PMID:12779323</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 22: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Craik, D J]]
+[[Category: Oldenlandia affinis]]
-[[Category: Gruber, C W]]
+[[Category: Craik DJ]]
-[[Category: Harvey, P J]]
+[[Category: Gruber CW]]
-[[Category: Cck motif]]
+[[Category: Harvey PJ]]
-[[Category: Cyclic peptide]]
-[[Category: Cyclotide]]
-[[Category: Knottin]]
-[[Category: Plant protein]]

7lhc

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Current revision

NMR Solution Structure of [T20K]kalata B1

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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