全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用:99美元

查看量下载量

相关文章

更多...
PLOS ONE  2014 

Cyclotide Structure–Activity Relationships: Qualitative and Quantitative Approaches Linking Cytotoxic and Anthelmintic Activity to the Clustering of Physicochemical Forces

DOI: 10.1371/journal.pone.0091430

Full-Text   Cite this paper   Add to My Lib

Abstract:

Cyclotides are a family of plant-derived proteins that are characterized by a cyclic backbone and a knotted disulfide topology. Their cyclic cystine knot (CCK) motif makes them exceptionally resistant to thermal, chemical, and enzymatic degradation. Cyclotides exert much of their biological activity via interactions with cell membranes. In this work, we qualitatively and quantitatively analyze the cytotoxic and anthelmintic membrane activities of cyclotides. The qualitative and quantitative models describe the potency of cyclotides using four simple physicochemical terms relevant to membrane contact. Specifically, surface areas of the cyclotides representing lipophilic and hydrogen bond donating properties were quantified and their distribution across the molecular surface was determined. The resulting quantitative structure-activity relation (QSAR) models suggest that the activity of the cyclotides is proportional to their lipophilic and positively charged surface areas, provided that the distribution of these surfaces is asymmetric. In addition, we qualitatively analyzed the physicochemical differences between the various cyclotide subfamilies and their effects on the cyclotides' orientation on the membrane and membrane activity.

References

[1]  Craik DJ, Daly NL, Bond T, Waine C (1999) Plant cyclotides: A unique family of cyclic and knotted proteins that defines the cyclic cystine knot structural motif. J Mol Biol 294: 1327–1336. doi: 10.1006/jmbi.1999.3383
[2]  G?ransson U, Burman R, Gunasekera S, Str?mstedt AA, Rosengren KJ (2012) Circular proteins from plants and fungi. J Biol Chem 287: 27001–27006. doi: 10.1074/jbc.r111.300129
[3]  Colgrave ML, Craik DJ (2004) Thermal, chemical, and enzymatic stability of the cyclotide kalata B1: the importance of the cyclic cystine knot. Biochemistry 43: 5965–5975. doi: 10.1021/bi049711q
[4]  Gruber CW, Elliott AG, Ireland DC, Delprete PG, Dessein S, et al. (2008) Distribution and evolution of circular miniproteins in flowering plants. Plant Cell 20: 2471–2483. doi: 10.1105/tpc.108.062331
[5]  Hashempour H, Koehbach J, Daly NL, Ghassempour A, Gruber CW (2013) Characterizing circular peptides in mixtures: sequence fragment assembly of cyclotides from a violet plant by MALDI-TOF/TOF mass spectrometry. Amino Acids 44: 581–595. doi: 10.1007/s00726-012-1376-x
[6]  Poth AG, Colgrave ML, Philip R, Kerenga B, Daly NL, et al. (2011) Discovery of cyclotides in the fabaceae plant family provides new insights into the cyclization, evolution, and distribution of circular proteins. ACS Chem Biol 6: 345–355. doi: 10.1021/cb100388j
[7]  Poth AG, Mylne JS, Grassl J, Lyons RE, Millar AH, et al. (2012) Cyclotides associate with leaf vasculature and are the products of a novel precursor in petunia (Solanaceae). J Biol Chem 287: 27033–27046. doi: 10.1074/jbc.m112.370841
[8]  Nguyen GK, Lian Y, Pang EW, Nguyen PQ, Tran TD, et al. (2013) Discovery of linear cyclotides in monocot plant Panicum laxum of Poaceae family provides new insights into evolution and distribution of cyclotides in plants. J Biol Chem 288: 3370–3380. doi: 10.1074/jbc.m112.415356
[9]  Craik DJ, Daly NL, Mulvenna J, Plan MR, Trabi M (2004) Discovery, structure and biological activities of the cyclotides. Curr Protein Pept Sci 5: 297–315. doi: 10.2174/1389203043379512
[10]  Jennings C, West J, Waine C, Craik D, Anderson M (2001) Biosynthesis and insecticidal properties of plant cyclotides: The cyclic knotted proteins from Oldenlandia affinis. Proc Natl Acad Sci U S A 98: 10614–10619. doi: 10.1073/pnas.191366898
[11]  Tam JP, Lu YA, Yang JL, Chiu KW (1999) An unusual structural motif of antimicrobial peptides containing end-to-end macrocycle and cystine-knot disulfides. Proc Natl Acad Sci U S A 96: 8913–8918. doi: 10.1073/pnas.96.16.8913
[12]  Ovesen RG, Brandt KK, G?ransson U, Nielsen J, Hansen HC, et al. (2011) Biomedicine in the environment: cyclotides constitute potent natural toxins in plants and soil bacteria. Environ Toxicol Chem 30: 1190–1196. doi: 10.1002/etc.496
[13]  Lindholm P, G?ransson U, Johansson S, Claeson P, Gullbo J, et al. (2002) Cyclotides: a novel type of cytotoxic agents. Mol Cancer Ther 1: 365–369.
[14]  Gustafson KR, Sowder RC, Henderson LE, Parsons IC, Kashman Y, et al. (1994) Circulins A and B. Novel Hiv-Inhibitory Macrocyclic Peptides from the Tropical Tree Chassalia parvifolia. J Am Chem Soc 116: 9337–9338. doi: 10.1021/ja00099a064
[15]  Aboye TL, Ha H, Majumder S, Christ F, Debyser Z, et al. (2012) Design of a novel cyclotide-based CXCR4 antagonist with anti-human immunodeficiency virus (HIV)-1 activity. J Med Chem 55: 10729–10734. doi: 10.1021/jm301468k
[16]  Daly NL, Clark RJ, Plan MR, Craik DJ (2006) Kalata B8, a novel antiviral circular protein, exhibits conformational flexibility in the cystine knot motif. Biochem J 393: 619–626. doi: 10.1042/bj20051371
[17]  Henriques ST, Huang YH, Rosengren KJ, Franquelim HG, Carvalho FA, et al. (2011) Decoding the membrane activity of the cyclotide kalata B1: the importance of phosphatidylethanolamine phospholipids and lipid organization on hemolytic and anti-HIV activities. J Biol Chem 286: 24231–24241. doi: 10.1074/jbc.m111.253393
[18]  Burman R, Herrmann A, Tran R, Kivela JE, Lomize A, et al. (2011) Cytotoxic potency of small macrocyclic knot proteins: Structure-activity and mechanistic studies of native and chemically modified cyclotides. Org Biomol Chem 9: 4306–4314. doi: 10.1039/c0ob00966k
[19]  Simonsen SM, Sando L, Rosengren KJ, Wang CK, Colgrave ML, et al. (2008) Alanine scanning mutagenesis of the prototypic cyclotide reveals a cluster of residues essential for bioactivity. J Biol Chem 283: 9805–9813. doi: 10.1074/jbc.m709303200
[20]  Huang YH, Colgrave ML, Clark RJ, Kotze AC, Craik DJ (2010) Lysine-scanning Mutagenesis Reveals an Amendable Face of the Cyclotide Kalata B1 for the Optimization of Nematocidal Activity. J Biol Chem 285: 10797–10805. doi: 10.1074/jbc.m109.089854
[21]  Wang CK, Colgrave ML, Ireland DC, Kaas Q, Craik DJ (2009) Despite a conserved cystine knot motif, different cyclotides have different membrane binding modes. Biophys J 97: 1471–1481. doi: 10.1016/j.bpj.2009.06.032
[22]  Herrmann A, Svangard E, Claeson P, Gullbo J, Bohlin L, et al. (2006) Key role of glutamic acid for the cytotoxic activity of the cyclotide cycloviolacin O2. Cell Mol Life Sci 63: 235–245. doi: 10.1007/s00018-005-5486-4
[23]  Ostberg N, Kaznessis Y (2005) Protegrin structure-activity relationships: using homology models of synthetic sequences to determine structural characteristics important for activity. Peptides 26: 197–206. doi: 10.1016/j.peptides.2004.09.020
[24]  Langham AA, Khandelia H, Schuster B, Waring AJ, Lehrer RI, et al. (2008) Correlation between simulated physicochemical properties and hemolycity of protegrin-like antimicrobial peptides: predicting experimental toxicity. Peptides 29: 1085–1093. doi: 10.1016/j.peptides.2008.03.018
[25]  Bhonsle JB, Venugopal D, Huddler DP, Magill AJ, Hicks RP (2007) Application of 3D-QSAR for identification of descriptors defining bioactivity of antimicrobial peptides. J Med Chem 50: 6545–6553. doi: 10.1021/jm070884y
[26]  Frecer V (2006) QSAR analysis of antimicrobial and haemolytic effects of cyclic cationic antimicrobial peptides derived from protegrin-1. Bioorg Med Chem 14: 6065–6074. doi: 10.1016/j.bmc.2006.05.005
[27]  Gouy M, Guindon S, Gascuel O (2010) SeaView version 4: A multiplatform graphical user interface for sequence alignment and phylogenetic tree building. Mol Biol Evol 27: 221–224. doi: 10.1093/molbev/msp259
[28]  Rosengren KJ, Daly NL, Plan MR, Waine C, Craik DJ (2003) Twists, knots, and rings in proteins. Structural definition of the cyclotide framework. J Biol Chem 278: 8606–8616. doi: 10.1074/jbc.m211147200
[29]  Jennings CV, Rosengren KJ, Daly NL, Plan M, Stevens J, et al. (2005) Isolation, solution structure, and insecticidal activity of kalata B2, a circular protein with a twist: do Mobius strips exist in nature? Biochemistry 44: 851–860. doi: 10.1021/bi047837h
[30]  Clark RJ, Daly NL, Craik DJ (2006) Structural plasticity of the cyclic-cystine-knot framework: implications for biological activity and drug design. Biochem J 394: 85–93. doi: 10.1042/bj20051691
[31]  Daly NL, Koltay A, Gustafson KR, Boyd MR, Casas-Finet JR, et al. (1999) Solution structure by NMR of circulin A: a macrocyclic knotted peptide having anti-HIV activity. J Mol Biol 285: 333–345. doi: 10.1006/jmbi.1998.2276
[32]  Koltay A, Daly NL, Gustafson KR, Craik DJ (2005) Structure of Circulin B and Implications for Antimicrobial Activity of the Cyclotides. Int J Pept Res Ther 11: 99–106. doi: 10.1007/s10989-004-1722-2
[33]  G?ransson U, Herrmann A, Burman R, Haugaard-Jonsson LM, Rosengren KJ (2009) The conserved glu in the cyclotide cycloviolacin O2 has a key structural role. Chembiochem 10: 2354–2360. doi: 10.1002/cbic.200900342
[34]  Ireland DC, Colgrave ML, Craik DJ (2006) A novel suite of cyclotides from Viola odorata: sequence variation and the implications for structure, function and stability. Biochem J 400: 1–12. doi: 10.1042/bj20060627
[35]  Wang CK, Hu SH, Martin JL, Sjogren T, Hajdu J, et al. (2009) Combined X-ray and NMR analysis of the stability of the cyclotide cystine knot fold that underpins its insecticidal activity and potential use as a drug scaffold. J Biol Chem 284: 10672–10683. doi: 10.1074/jbc.m900021200
[36]  Trabi M, Craik DJ (2004) Tissue-specific expression of head-to-tail cyclized miniproteins in Violaceae and structure determination of the root cyclotide Viola hederacea root cyclotide1. Plant Cell 16: 2204–2216. doi: 10.1105/tpc.104.021790
[37]  Mulvenna JP, Sando L, Craik DJ (2005) Processing of a 22 kDa precursor protein to produce the circular protein tricyclon A. Structure 13: 691–701. doi: 10.1016/j.str.2005.02.013
[38]  Ireland DC, Colgrave ML, Nguyencong P, Daly NL, Craik DJ (2006) Discovery and characterization of a linear cyclotide from Viola odorata: implications for the processing of circular proteins. J Mol Biol 357: 1522–1535. doi: 10.1016/j.jmb.2006.01.051
[39]  Sali A, Blundell TL (1993) Comparative Protein Modeling by Satisfaction of Spatial Restraints. J Mol Biol 234: 779–815. doi: 10.1006/jmbi.1993.1626
[40]  Labute P (2010) LowModeMD—implicit low-mode velocity filtering applied to conformational search of macrocycles and protein loops. J Chem Inf Model 50: 792–800. doi: 10.1021/ci900508k
[41]  Molecular Operating Environment (2012) 10. 1010 Sherbooke St. West, Suite #910, Montreal, QC, Canada, H3A 2R7: Chemical Computing Group Inc., 2012.
[42]  Molinspiration Cheminformatics (2014) www.molinspiration.com/cgi-bin/propertie?s
[43]  Lee B, Richards FM (1971) Interpretation of Protein Structures - Estimation of Static Accessibility. J Mol Biol 55: 379–400. doi: 10.1016/0022-2836(71)90324-x
[44]  Discovery Studio Modeling Environment (2007) Release 6.0 San Diego: Accelrys Software Inc.
[45]  Minitab Inc. (2010) Minitab 16 statistical Software. State College, PA
[46]  Str?mstedt AA, Ringstad L, Schmidtchen A, Malmsten M (2010) Interaction between amphiphilic peptides and phospholipid membranes. Current Opinion in Colloid & Interface Science 15: 467–478. doi: 10.1016/j.cocis.2010.05.006
[47]  Yeshak MY, Burman R, Asres K, G?ransson U (2011) Cyclotides from an Extreme Habitat: Characterization of Cyclic Peptides from Viola abyssinica of the Ethiopian Highlands. J Nat Prod 74: 727–731. doi: 10.1021/np100790f
[48]  Gerlach SL, Burman R, Bohlin L, Mondal D, G?ransson U (2010) Isolation, Characterization, and Bioactivity of Cyclotides from the Micronesian Plant Psychotria leptothyrsa. J Nat Prod 73: 1207–1213. doi: 10.1021/np9007365
[49]  Herrmann A, Burman R, Mylne JS, Karlsson G, Gullbo J, et al. (2008) The alpine violet, Viola biflora, is a rich source of cyclotides with potent cytotoxicity. Phytochemistry 69: 939–952. doi: 10.1016/j.phytochem.2007.10.023
[50]  Svangard E, G?ransson U, Hocaoglu Z, Gullbo J, Larsson R, et al. (2004) Cytotoxic cyclotides from Viola tricolor. J Nat Prod 67: 144–147. doi: 10.1021/np030101l
[51]  Colgrave ML, Kotze AC, Ireland DC, Wang CK, Craik DJ (2008) The anthelmintic activity of the cyclotides: Natural variants with enhanced activity. Chembiochem 9: 1939–1945. doi: 10.1002/cbic.200800174
[52]  Bowie JU, Luthy R, Eisenberg D (1991) A method to identify protein sequences that fold into a known three-dimensional structure. Science 253: 164–170. doi: 10.1126/science.1853201
[53]  Jones DT, Taylor WR, Thornton JM (1992) A new approach to protein fold recognition. Nature 358: 86–89. doi: 10.1038/358086a0
[54]  Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215: 403–410. doi: 10.1016/s0022-2836(05)80360-2
[55]  Pearson WR (1990) Rapid and sensitive sequence comparison with FASTP and FASTA. Methods Enzymol 183: 63–98. doi: 10.1016/0076-6879(90)83007-v
[56]  Morris AL, Macarthur MW, Hutchinson EG, Thornton JM (1992) Stereochemical Quality of Protein-Structure Coordinates. Proteins-Structure Function and Genetics 12: 345–364. doi: 10.1002/prot.340120407
[57]  Kyte J, Doolittle RF (1982) A simple method for displaying the hydropathic character of a protein. J Mol Biol 157: 105–132. doi: 10.1016/0022-2836(82)90515-0
[58]  Black SD, Mould DR (1991) Development of hydrophobicity parameters to analyze proteins which bear post- or cotranslational modifications. Anal Biochem 193: 72–82. doi: 10.1016/0003-2697(91)90045-u
[59]  van de Waterbeemd H, Karajiannis H, Eltayar N (1994) Lipophilicity of Amino-Acids. Amino Acids 7: 129–145. doi: 10.1007/bf00814156
[60]  de Planque MR, Bonev BB, Demmers JA, Greathouse DV, Koeppe RE 2nd, et al. (2003) Interfacial anchor properties of tryptophan residues in transmembrane peptides can dominate over hydrophobic matching effects in peptide-lipid interactions. Biochemistry 42: 5341–5348. doi: 10.1021/bi027000r
[61]  Yau WM, Wimley WC, Gawrisch K, White SH (1998) The preference of tryptophan for membrane interfaces. Biochemistry 37: 14713–14718. doi: 10.1021/bi980809c
[62]  Berendsen HJC, Postma JPM, van Gunsteren WF, Hermans J (1981) In Intermolecular Forces, edited by Pullman B: D. Reidel publishing company. pp. 331–342.
[63]  Lomize MA, Lomize AL, Pogozheva ID, Mosberg HI (2006) OPM: orientations of proteins in membranes database. Bioinformatics 22: 623–625. doi: 10.1093/bioinformatics/btk023
[64]  Chen Y, Guarnieri MT, Vasil AI, Vasil ML, Mant CT, et al. (2007) Role of peptide hydrophobicity in the mechanism of action of alpha-helical antimicrobial peptides. Antimicrob Agents Chemother 51: 1398–1406. doi: 10.1128/aac.00925-06
[65]  Koehbach J, O'Brien M, Muttenthaler M, Miazzo M, Akcan M, et al. (2013) Oxytocic plant cyclotides as templates for peptide G protein-coupled receptor ligand design. Proc Natl Acad Sci U S A 110: 21183–21188. doi: 10.1073/pnas.1311183110
[66]  Hall LH, Kier LB (1991) The Molecular Connectivity Chi Indexes and Kappa Shape Indexes in Structure-Property Modeling. Reviews in Computational Chemistry 2: 367–422. doi: 10.1002/9780470125793.ch9
[67]  Burman R, Str?mstedt AA, Malmsten M, G?ransson U (2011) Cyclotide-membrane interactions: defining factors of membrane binding, depletion and disruption. Biochim Biophys Acta 1808: 2665–2673. doi: 10.1016/j.bbamem.2011.07.004
[68]  Wang CK, Clark RJ, Harvey PJ, Rosengren KJ, Cemazar M, et al. (2011) The role of conserved Glu residue on cyclotide stability and activity: a structural and functional study of kalata B12, a naturally occurring Glu to Asp mutant. Biochemistry 50: 4077–4086. doi: 10.1021/bi2004153
[69]  Rogers D (1994) Application of genetic function approximation to quantitative structure-activity relationship and quantitative structure-property relationships. J Chem Inf Comput Sci 34: 854–866. doi: 10.1021/ci00020a020

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133