Conformational change in the thiazole and oxazoline containing cyclic octapeptides, the patellamides. Part 1. Cu2+ and Zn2+ induced conformational change

L A Morris, B F Milne, G S Thompson, M Jaspars

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24 Citations (Scopus)

Abstract

Conformational change during the binding of Cu2+ and Zn2+ to the thiazole and oxazoline containing cyclic octapeptides, the patellamides, is examined by a combination of experimental and theoretical methods. Circular dichroism and NOE-restrained molecular dynamics studies indicate that upon complexing with one equivalent of Cu2+, patellamide C undergoes a change in conformation which pre-organises a second Cu2+ binding site, and that the binding of a second Cu2+ induces no further conformational change. The binding of Zn2+ induces little conformational change in patellamide C. A restrained conformational search shows that the conformational change induced by the addition of one equivalent of Cu2+ to patellamide C is an intrinsic design feature of the system. Electronic structure calculations indicate that the patellamides provide an ideal coordination environment for Cu2+. On the basis of the evidence gathered, it can be proposed that Cu2+ is the biologically relevant metal for the patellamides.

Original languageEnglish
Pages (from-to)1072-1075
Number of pages4
JournalJournal of the Chemical Society, Perkin Transactions 2
DOIs
Publication statusPublished - 2002

Keywords

  • INTERPROTON DISTANCE RESTRAINTS
  • COMPACT EFFECTIVE POTENTIALS
  • EXPONENT BASIS-SETS
  • LISSOCLINUM-PATELLA
  • MOLECULAR-DYNAMICS
  • NMR-SPECTROSCOPY
  • METAL-BINDING
  • ASCIDIACYCLAMIDE
  • PEPTIDE
  • METABOLITES

Cite this

@article{6e278a8b75bf42669fd4ea5c68aca30b,
title = "Conformational change in the thiazole and oxazoline containing cyclic octapeptides, the patellamides. Part 1. Cu2+ and Zn2+ induced conformational change",
abstract = "Conformational change during the binding of Cu2+ and Zn2+ to the thiazole and oxazoline containing cyclic octapeptides, the patellamides, is examined by a combination of experimental and theoretical methods. Circular dichroism and NOE-restrained molecular dynamics studies indicate that upon complexing with one equivalent of Cu2+, patellamide C undergoes a change in conformation which pre-organises a second Cu2+ binding site, and that the binding of a second Cu2+ induces no further conformational change. The binding of Zn2+ induces little conformational change in patellamide C. A restrained conformational search shows that the conformational change induced by the addition of one equivalent of Cu2+ to patellamide C is an intrinsic design feature of the system. Electronic structure calculations indicate that the patellamides provide an ideal coordination environment for Cu2+. On the basis of the evidence gathered, it can be proposed that Cu2+ is the biologically relevant metal for the patellamides.",
keywords = "INTERPROTON DISTANCE RESTRAINTS, COMPACT EFFECTIVE POTENTIALS, EXPONENT BASIS-SETS, LISSOCLINUM-PATELLA, MOLECULAR-DYNAMICS, NMR-SPECTROSCOPY, METAL-BINDING, ASCIDIACYCLAMIDE, PEPTIDE, METABOLITES",
author = "Morris, {L A} and Milne, {B F} and Thompson, {G S} and M Jaspars",
year = "2002",
doi = "10.1039/b202823n",
language = "English",
pages = "1072--1075",
journal = "Journal of the Chemical Society, Perkin Transactions 2",
issn = "1472-779X",
publisher = "Royal Society of Chemistry",

}

TY - JOUR

T1 - Conformational change in the thiazole and oxazoline containing cyclic octapeptides, the patellamides. Part 1. Cu2+ and Zn2+ induced conformational change

AU - Morris, L A

AU - Milne, B F

AU - Thompson, G S

AU - Jaspars, M

PY - 2002

Y1 - 2002

N2 - Conformational change during the binding of Cu2+ and Zn2+ to the thiazole and oxazoline containing cyclic octapeptides, the patellamides, is examined by a combination of experimental and theoretical methods. Circular dichroism and NOE-restrained molecular dynamics studies indicate that upon complexing with one equivalent of Cu2+, patellamide C undergoes a change in conformation which pre-organises a second Cu2+ binding site, and that the binding of a second Cu2+ induces no further conformational change. The binding of Zn2+ induces little conformational change in patellamide C. A restrained conformational search shows that the conformational change induced by the addition of one equivalent of Cu2+ to patellamide C is an intrinsic design feature of the system. Electronic structure calculations indicate that the patellamides provide an ideal coordination environment for Cu2+. On the basis of the evidence gathered, it can be proposed that Cu2+ is the biologically relevant metal for the patellamides.

AB - Conformational change during the binding of Cu2+ and Zn2+ to the thiazole and oxazoline containing cyclic octapeptides, the patellamides, is examined by a combination of experimental and theoretical methods. Circular dichroism and NOE-restrained molecular dynamics studies indicate that upon complexing with one equivalent of Cu2+, patellamide C undergoes a change in conformation which pre-organises a second Cu2+ binding site, and that the binding of a second Cu2+ induces no further conformational change. The binding of Zn2+ induces little conformational change in patellamide C. A restrained conformational search shows that the conformational change induced by the addition of one equivalent of Cu2+ to patellamide C is an intrinsic design feature of the system. Electronic structure calculations indicate that the patellamides provide an ideal coordination environment for Cu2+. On the basis of the evidence gathered, it can be proposed that Cu2+ is the biologically relevant metal for the patellamides.

KW - INTERPROTON DISTANCE RESTRAINTS

KW - COMPACT EFFECTIVE POTENTIALS

KW - EXPONENT BASIS-SETS

KW - LISSOCLINUM-PATELLA

KW - MOLECULAR-DYNAMICS

KW - NMR-SPECTROSCOPY

KW - METAL-BINDING

KW - ASCIDIACYCLAMIDE

KW - PEPTIDE

KW - METABOLITES

U2 - 10.1039/b202823n

DO - 10.1039/b202823n

M3 - Article

SP - 1072

EP - 1075

JO - Journal of the Chemical Society, Perkin Transactions 2

JF - Journal of the Chemical Society, Perkin Transactions 2

SN - 1472-779X

ER -