TY - JOUR
T1 - The second type II module from human matrix metalloproteinase 2
T2 - Structure, function and dynamics
AU - Briknarová, Klára
AU - Grishaev, Alexander
AU - Bányai, László
AU - Tordai, Hedvig
AU - Patthy, László
AU - Llinás, Miguel
N1 - Funding Information:
We thank Daniel N Marti for computer help, András Patthy for protein sequence analysis and peptide synthesis, Gordon S Rule for pulse programs, Johann Schaller for ESI-MS analysis, and Virgil Simplaceanu for technical assistance with NMR spectrometers. This work was supported by NIH grant HL29409 and grants OTKA 323 and OTKA T 5211 from the Hungarian Academy of Sciences.
PY - 1999/10/15
Y1 - 1999/10/15
N2 - Background: Matrix metalloproteinase 2 (MMP-2, gelatinase A, 72 kDa type IV collagenase) has an important role in extracellular matrix degradation during cell migration and tissue remodeling. It is involved in development, inflammation, wound healing, tumor invasion, metastasis and other physiological and pathological processes. The enzyme cleaves several types of collagen, elastin, fibronectin and laminin. Binding to collagen is mediated by three repeats homologous to fibronectin type II modules, which are inserted in the catalytic domain in proximity to the active site. Results: We have determined the NMR solution structure of the second type II module from human MMP-2 (col-2). The module exhibits a typical type II fold with two short double-stranded antiparallel β sheets and three large loops packed around a cluster of conserved aromatic residues. Backbone amide dynamics, derived from 15N relaxation experiments, correlate well with solvent accessibility and intramolecular hydrogen bonding. A synthetic peptide with the collagen consensus sequence, (Pro-Pro-Gly)6, is shown to interact with the module. Conclusions: Spectral perturbations induced by (Pro-Pro-Gly)6 binding reveal the region involved in the interaction of col-2 with collagen. The binding surface comprises exposed aromatic residues Phe21, Tyr38, Trp40, Tyr47, Tyr53 and Phe55, and the neighboring Gly33-Gly37 segment.
AB - Background: Matrix metalloproteinase 2 (MMP-2, gelatinase A, 72 kDa type IV collagenase) has an important role in extracellular matrix degradation during cell migration and tissue remodeling. It is involved in development, inflammation, wound healing, tumor invasion, metastasis and other physiological and pathological processes. The enzyme cleaves several types of collagen, elastin, fibronectin and laminin. Binding to collagen is mediated by three repeats homologous to fibronectin type II modules, which are inserted in the catalytic domain in proximity to the active site. Results: We have determined the NMR solution structure of the second type II module from human MMP-2 (col-2). The module exhibits a typical type II fold with two short double-stranded antiparallel β sheets and three large loops packed around a cluster of conserved aromatic residues. Backbone amide dynamics, derived from 15N relaxation experiments, correlate well with solvent accessibility and intramolecular hydrogen bonding. A synthetic peptide with the collagen consensus sequence, (Pro-Pro-Gly)6, is shown to interact with the module. Conclusions: Spectral perturbations induced by (Pro-Pro-Gly)6 binding reveal the region involved in the interaction of col-2 with collagen. The binding surface comprises exposed aromatic residues Phe21, Tyr38, Trp40, Tyr47, Tyr53 and Phe55, and the neighboring Gly33-Gly37 segment.
KW - Collagen
KW - Fibronectin type II module
KW - Gelatinase A
KW - Matrix metalloproteinase 2
KW - Type IV collagenase
UR - http://www.scopus.com/inward/record.url?scp=0033569704&partnerID=8YFLogxK
U2 - 10.1016/S0969-2126(00)80057-X
DO - 10.1016/S0969-2126(00)80057-X
M3 - Article
C2 - 10545322
AN - SCOPUS:0033569704
SN - 0969-2126
VL - 7
SP - 1235
EP - 1245
JO - Structure
JF - Structure
IS - 10
ER -