1ma4: Difference between revisions
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< | ==Solution Structure of Tachyplesin I Mutant TPY4 in water== | ||
<StructureSection load='1ma4' size='340' side='right'caption='[[1ma4]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1ma4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Tachypleus_tridentatus Tachypleus tridentatus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MA4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MA4 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1ma4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ma4 OCA], [https://pdbe.org/1ma4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ma4 RCSB], [https://www.ebi.ac.uk/pdbsum/1ma4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ma4 ProSAT]</span></td></tr> | ||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/TAC1_TACTR TAC1_TACTR] Significantly inhibits the growth of Gram-negative and Gram-positive bacteria. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Tachyplesin I is a 17-residue peptide isolated from the horseshoe crab, Tachypleus tridentatus.It has high antimicrobial activity and adopts a beta-hairpin conformation in solution stabilized by two cross-strand disulfide bonds. We report an NMR structural investigation of wild-type tachyplesin I and three linear derivatives (denoted TPY4, TPF4, and TPA4 in which the bridging cysteine residues are uniformly replaced with tyrosine, phenylalanine, and alanine, respectively). The three-dimensional aqueous solution structures of the wild type and the active variant TPY4 reveal very similar beta-hairpin conformations. In contrast, the inactive variant TPA4 is unstructured in solution. The arrangement of the tyrosine side chains in the TPY4 structure suggests that the beta-hairpin is stabilized by aromatic ring stacking interactions. This is supported by experiments in which the beta-hairpin structure of TPF4 is disrupted by the addition of phenol, but not by the addition of an equimolar amount of cyclohexanol. We have also determined the structures of wild-type tachyplesin I and TPY4 in the presence of dodecylphosphocholine micelles. Both peptides undergo significant conformational rearrangement upon micelle association. Analysis of the micelle-associated peptide structures shows an increased level of exposure of specific hydrophobic side chains and an increased hydrophobic integy moment. Comparison of the structures in micelle and aqueous solution for both wild-type tachyplesin I and TPY4 reveals two requirements for high antimicrobial activity: a beta-hairpin fold in solution and the ability to rearrange critical side chain residues upon membrane association. | |||
Solution and micelle-bound structures of tachyplesin I and its active aromatic linear derivatives.,Laederach A, Andreotti AH, Fulton DB Biochemistry. 2002 Oct 15;41(41):12359-68. PMID:12369825<ref>PMID:12369825</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1ma4" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Tachyplesin|Tachyplesin]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Large Structures]] | ||
[[Category: Tachypleus tridentatus]] | |||
[[Category: Andreotti AH]] | |||
== | [[Category: Fulton DB]] | ||
[[Category: Laederach A]] | |||
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Latest revision as of 14:23, 2 August 2023
Solution Structure of Tachyplesin I Mutant TPY4 in waterSolution Structure of Tachyplesin I Mutant TPY4 in water
Structural highlights
FunctionTAC1_TACTR Significantly inhibits the growth of Gram-negative and Gram-positive bacteria. Publication Abstract from PubMedTachyplesin I is a 17-residue peptide isolated from the horseshoe crab, Tachypleus tridentatus.It has high antimicrobial activity and adopts a beta-hairpin conformation in solution stabilized by two cross-strand disulfide bonds. We report an NMR structural investigation of wild-type tachyplesin I and three linear derivatives (denoted TPY4, TPF4, and TPA4 in which the bridging cysteine residues are uniformly replaced with tyrosine, phenylalanine, and alanine, respectively). The three-dimensional aqueous solution structures of the wild type and the active variant TPY4 reveal very similar beta-hairpin conformations. In contrast, the inactive variant TPA4 is unstructured in solution. The arrangement of the tyrosine side chains in the TPY4 structure suggests that the beta-hairpin is stabilized by aromatic ring stacking interactions. This is supported by experiments in which the beta-hairpin structure of TPF4 is disrupted by the addition of phenol, but not by the addition of an equimolar amount of cyclohexanol. We have also determined the structures of wild-type tachyplesin I and TPY4 in the presence of dodecylphosphocholine micelles. Both peptides undergo significant conformational rearrangement upon micelle association. Analysis of the micelle-associated peptide structures shows an increased level of exposure of specific hydrophobic side chains and an increased hydrophobic integy moment. Comparison of the structures in micelle and aqueous solution for both wild-type tachyplesin I and TPY4 reveals two requirements for high antimicrobial activity: a beta-hairpin fold in solution and the ability to rearrange critical side chain residues upon membrane association. Solution and micelle-bound structures of tachyplesin I and its active aromatic linear derivatives.,Laederach A, Andreotti AH, Fulton DB Biochemistry. 2002 Oct 15;41(41):12359-68. PMID:12369825[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
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