Construction of a 3D model of oligopeptidase B, a potential processing enzyme in prokaryotes

Tímea Gérczei, György M. Keserü, G. Náray-Szabó

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

A three dimensional structural model of oligopeptidase B (OpB) was constructed by homology modeling. High resolution X-ray structure of prolyl oligopeptidase (PEP), the only protein with sequential and functional homology was used as a template. Initial models of OpB were built by the MODELLER and were analysed by the PROCHECK programs. The best quality model was chosen for further refinement by two different techniques - either constrained molecular dynamics simulations or simulated annealing calculations starting from 500 K. The overall quality of each of the refined models was evaluated and the simulated annealing procedure found to be more effective. The refined model was analysed by different protein analysis programs including PROCHECK for the evaluation of the Ramachandran plot quality, PROSA for testing interaction energies and WHATIF for the calculation of packing quality. This structure was found to be satisfactory and also stable at room temperature as demonstrated by a 300 ps long unconstrained molecular dynamics simulation. Calculation of molecular electrostatic potentials revealed that the binding site of OpB is more negative than that of PEP, in accordance with the experimentally observed selectivity of OpB towards proteolysis at dibasic sites. A recently developed Monte Carlo docking method was used provide a structural rationale for the affinity differences measured between Z-Arg and Z-Arg-Arg substrates.

Original languageEnglish
Pages (from-to)7-17
Number of pages11
JournalJournal of Molecular Graphics and Modelling
Volume18
Issue number1
DOIs
Publication statusPublished - 2000

Fingerprint

oligopeptidase B
prokaryotes
enzymes
Enzymes
prolyl oligopeptidase
Processing
homology
simulated annealing
Simulated annealing
Molecular dynamics
Proteolysis
molecular dynamics
proteins
Proteins
Computer simulation
Binding sites
affinity
Electrostatics
templates
simulation

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Spectroscopy
  • Atomic and Molecular Physics, and Optics

Cite this

Construction of a 3D model of oligopeptidase B, a potential processing enzyme in prokaryotes. / Gérczei, Tímea; Keserü, György M.; Náray-Szabó, G.

In: Journal of Molecular Graphics and Modelling, Vol. 18, No. 1, 2000, p. 7-17.

Research output: Contribution to journalArticle

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