Modelling the structure of latexin-carboxypeptidase A complex based on chemical cross-linking and molecular docking

Date

2006

Authors

Mouradov, Dmitri
Craven, Ari
Forwood, Jade
Flanagan, Jack U
Garcia-Castellanos, Raquel
Gomis-Ruth, F. Xavier
Hume, D A
Martin, Jennifer Louise
Kobe, Bostjan
Huber, Thomas

Journal Title

Journal ISSN

Volume Title

Publisher

Oxford University Press

Abstract

We have determined the three-dimensional structure of the protein complex between latexin and carboxypeptidase A using a combination of chemical cross-linking, mass spectrometry and molecular docking. The locations of three intermolecular cross-links were identified using mass spectrometry and these constraints were used in combination with a speed-optimised docking algorithm allowing us to evaluate more than 3 × 1011 possible conformations. While cross-links represent only limited structural constraints, the combination of only three experimental cross-links with very basic molecular docking was sufficient to determine the complex structure. The crystal structure of the complex between latexin and carboxypeptidase A4 determined recently allowed us to assess the success of this structure determination approach. Our structure was shown to be within 4 Å r.m.s. deviation of Cα atoms of the crystal structure. The study demonstrates that cross-linking in combination with mass spectrometry can lead to efficient and accurate structural modelling of protein complexes.

Description

Keywords

Keywords: Chemical cross-linking; Latexin-carboxypeptidaseA; Molecular docking; Protein complex structure; Algorithms; Complexation; Crosslinking; Mass spectrometry; Mathematical models; Molecular structure; Enzymes; carboxypeptidase; protein; algorithm; article; a Chemical cross-linking; Latexin-carboxypeptidaseA; Mass spectrometry; Molecular docking; Protein complex structure

Citation

Source

Protein Engineering Design and Selection

Type

Journal article

Book Title

Entity type

Access Statement

License Rights

DOI

10.1093/protein/gzi070

Restricted until

2037-12-31