Informacja

Drogi użytkowniku, aplikacja do prawidłowego działania wymaga obsługi JavaScript. Proszę włącz obsługę JavaScript w Twojej przeglądarce.

Przeglądasz jako GOŚĆ
Tytuł pozycji:

Computational design and characterization of nanobody-derived peptides that stabilize the active conformation of the β 2 -adrenergic receptor (β 2 -AR).

Tytuł :
Computational design and characterization of nanobody-derived peptides that stabilize the active conformation of the β 2 -adrenergic receptor (β 2 -AR).
Autorzy :
Sencanski M; Center for Multidisciplinary Research, Institute of Nuclear Sciences VINCA, University of Belgrade, Belgrade, Serbia.
Glisic S; Center for Multidisciplinary Research, Institute of Nuclear Sciences VINCA, University of Belgrade, Belgrade, Serbia.
Šnajder M; Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia.
Veljkovic N; Center for Multidisciplinary Research, Institute of Nuclear Sciences VINCA, University of Belgrade, Belgrade, Serbia.
Poklar Ulrih N; Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia.
Mavri J; Laboratory of Computational Biochemistry and Drug Design, National Institute of Chemistry, Ljubljana, Slovenia.
Vrecl M; Institute of Preclinical Sciences, Veterinary Faculty, University of Ljubljana, Ljubljana, Slovenia. .
Pokaż więcej
Źródło :
Scientific reports [Sci Rep] 2019 Nov 12; Vol. 9 (1), pp. 16555. Date of Electronic Publication: 2019 Nov 12.
Typ publikacji :
Journal Article; Research Support, Non-U.S. Gov't
Język :
English
Imprint Name(s) :
Original Publication: London : Nature Publishing Group, copyright 2011-
MeSH Terms :
Peptides/*chemistry
Receptors, Adrenergic, beta-2/*metabolism
HEK293 Cells ; Humans ; Ligands ; Molecular Dynamics Simulation ; Protein Binding ; Protein Domains ; Protein Stability ; Single-Domain Antibodies
References :
J Recept Signal Transduct Res. 2006;26(5-6):505-26. (PMID: 17118796)
J Biomol Screen. 2009 Apr;14(4):371-80. (PMID: 19403920)
J Comput Chem. 2010 Mar;31(4):671-90. (PMID: 19575467)
Nucleic Acids Res. 2015 Jul 1;43(W1):W419-24. (PMID: 25943545)
Mol Pharmacol. 2014 Mar;85(3):472-81. (PMID: 24319111)
Nature. 2015 Jul 30;523(7562):561-7. (PMID: 26200343)
J Comput Chem. 2012 Dec 5;33(31):2451-68. (PMID: 22821581)
Nat Rev Drug Discov. 2017 Dec;16(12):829-842. (PMID: 29075003)
Nature. 2013 Oct 24;502(7472):575-579. (PMID: 24056936)
J Biol Chem. 2001 Jul 13;276(28):26285-90. (PMID: 11342547)
Nature. 2018 Jul;559(7712):45-53. (PMID: 29973731)
J Mol Graph. 1996 Feb;14(1):33-8, 27-8. (PMID: 8744570)
J Comput Chem. 2004 Aug;25(11):1400-15. (PMID: 15185334)
Sci Rep. 2015 Jun 19;5:11434. (PMID: 26091504)
Nature. 2007 Nov 15;450(7168):383-7. (PMID: 17952055)
Annu Rev Pharmacol Toxicol. 2017 Jan 6;57:19-37. (PMID: 27959623)
J Biomol Screen. 2004 Jun;9(4):322-33. (PMID: 15191649)
Nature. 2011 Jul 19;477(7366):549-55. (PMID: 21772288)
Nanomedicine (Lond). 2013 Jun;8(6):1013-26. (PMID: 23730699)
J Biomol Screen. 2007 Feb;12(1):41-9. (PMID: 17114329)
J Comput Chem. 2005 Dec;26(16):1781-802. (PMID: 16222654)
J Biol Chem. 2002 Mar 15;277(11):9043-8. (PMID: 11782458)
PLoS One. 2014 Nov 17;9(11):e112664. (PMID: 25401701)
J Phys Chem B. 1998 Apr 30;102(18):3586-616. (PMID: 24889800)
BMC Struct Biol. 2009 Sep 28;9:62. (PMID: 19785758)
Nat Chem Biol. 2012 Jul 18;8(8):670-3. (PMID: 22810761)
Science. 2000 Aug 4;289(5480):739-45. (PMID: 10926528)
Science. 2007 Nov 23;318(5854):1258-65. (PMID: 17962520)
Eur J Biochem. 1995 Sep 1;232(2):464-72. (PMID: 7556195)
BMC Genomics. 2011 Jan 07;12:14. (PMID: 21214938)
Nature. 2011 Jan 13;469(7329):175-80. (PMID: 21228869)
Chemistry. 2017 Jul 18;23(40):9632-9640. (PMID: 28449310)
Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12562-6. (PMID: 12271136)
Curr Protein Pept Sci. 2008 Oct;9(5):493-506. (PMID: 18855700)
Nat Rev Drug Discov. 2013 Jan;12(1):25-34. (PMID: 23237917)
Int J Mol Sci. 2016 Jul 19;17(7):. (PMID: 27447620)
Curr Opin Struct Biol. 2011 Aug;21(4):567-72. (PMID: 21782416)
Methods Mol Biol. 2015;1278:239-65. (PMID: 25859954)
Biochemistry. 2002 Mar 12;41(10):3321-8. (PMID: 11876640)
Phys Rev Lett. 2008 Jan 18;100(2):020603. (PMID: 18232845)
Expert Opin Drug Discov. 2011 Dec;6(12):1263-70. (PMID: 22647065)
Matrix Biol. 2008 Mar;27(2):96-106. (PMID: 17988845)
Immunity. 2000 Jul;13(1):37-45. (PMID: 10933393)
Annu Rev Pharmacol Toxicol. 2013;53:531-56. (PMID: 23140243)
Methods. 2018 Aug 15;146:107-119. (PMID: 29438829)
Substance Nomenclature :
0 (Ligands)
0 (Peptides)
0 (Receptors, Adrenergic, beta-2)
0 (Single-Domain Antibodies)
Entry Date(s) :
Date Created: 20191114 Date Completed: 20201029 Latest Revision: 20210110
Update Code :
20210623
PubMed Central ID :
PMC6851183
DOI :
10.1038/s41598-019-52934-8
PMID :
31719570
Czasopismo naukowe
This study aimed to design and functionally characterize peptide mimetics of the nanobody (Nb) related to the β 2 -adrenergic receptor (β 2 -AR) (nanobody-derived peptide, NDP). We postulated that the computationally derived and optimized complementarity-determining region 3 (CDR3) of Nb is sufficient for its interaction with receptor. Sequence-related Nb-families preferring the agonist-bound active conformation of β 2 -AR were analysed using the informational spectrum method (ISM) and β 2 -AR:NDP complexes studied using protein-peptide docking and molecular dynamics (MD) simulations in conjunction with metadynamics calculations of free energy binding. The selected NDP of Nb71, designated P3, was 17 amino acids long and included CDR3. Metadynamics calculations yielded a binding free energy for the β 2 -AR:P3 complex of ΔG = (-7.23 ± 0.04) kcal/mol, or a Kd of (7.9 ± 0.5) μM, for T = 310 K. In vitro circular dichroism (CD) spectropolarimetry and microscale thermophoresis (MST) data provided additional evidence for P3 interaction with agonist-activated β 2 -AR, which displayed ~10-fold higher affinity for P3 than the unstimulated receptor (MST-derived EC 50 of 3.57 µM vs. 58.22 µM), while its ability to inhibit the agonist-induced interaction of β 2 -AR with β-arrestin 2 was less evident. In summary, theoretical and experimental evidence indicated that P3 preferentially binds agonist-activated β 2 -AR.
Zaloguj się, aby uzyskać dostęp do pełnego tekstu.

Ta witryna wykorzystuje pliki cookies do przechowywania informacji na Twoim komputerze. Pliki cookies stosujemy w celu świadczenia usług na najwyższym poziomie, w tym w sposób dostosowany do indywidualnych potrzeb. Korzystanie z witryny bez zmiany ustawień dotyczących cookies oznacza, że będą one zamieszczane w Twoim komputerze. W każdym momencie możesz dokonać zmiany ustawień dotyczących cookies