ISSN:
1573-3904
Keywords:
cFP
;
conformational analysis
;
dynamicssimulations
;
EP24.15
;
ROESY
;
thimet oligopeptidase
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract The enzyme thimet oligopeptidase (EC3.4.24.15, EP24.15) is responsible for the hydrolysis of a number of neuropeptides. Despite much research examining its substrate specificity, little is known about the conformational requirements of its active site. We have used 1D 1H and 2D TOCSY NMR experiments to assign the proton resonances of the EP24.15 inhibitor, N-[1-(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Tyr-p-aminobenzoate (cFP), and 2D ROESY NMR to investigate whether cFP exhibits any conformational preferences in CD3OD and in aqueous CD3OD. Molecular modelling of charged cFP in the gaseous phase generated a number of conformations that were consistent with the NMR data obtained in CD3OD. Analogous modelling on the uncharged cFP did not result in conformations consistent with any of the NMR data, but did suggest that, under non-polar conditions, cFP could adopt a hairpin conformation which would allow simultaneous coordination of the two carboxyl groups of cFP to the zinc ion in the active site of EP24.15.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1008946222327
Permalink
