PMID- 16085117
OWN - NLM
STAT- MEDLINE
DCOM- 20051228
LR  - 20061115
IS  - 0369-8114 (Print)
IS  - 0369-8114 (Linking)
VI  - 53
IP  - 7
DP  - 2005 Sep
TI  - Fibronectin type II (FnII)-like modules regulate gelatinase A activity.
PG  - 405-10
AB  - Gelatinase A, a member of the matrix metalloproteinase family, contains three 
      fibronectin type II (FnII)-like modules that are inserted within its catalytic 
      domain. These FnII modules, defined as exosites, play an essential role in 
      targeting the enzyme to matrix macromolecules, a process which can down-regulate 
      membrane-type metalloproteinase-driven progelatinase A activation. The 
      exosite/substrate-directed gelatinase inhibitors has been proposed as an 
      alternative approach to disappointing active site-directed inhibitors, to control 
      gelatinase A activity. In preliminary experiments, we evidenced that long-chain 
      unsaturated fatty acids could bind preferentially to the first FnII module of 
      gelatinase A. This interaction inhibits the activity of this enzyme towards 
      proteins (type I gelatin and collagen) and an octapeptide substrate, with K(i) in 
      the micromolar range. Since gelatinase A-catalyzed matrix proteolysis might 
      display a positive or negative influence (depending on the substrate cleaved), 
      the design of exosite-specific compounds for noncatalytic targeting of gelatinase 
      A would necessitate an extensive degradomic analysis.
FAU - Hornebeck, W
AU  - Hornebeck W
AD  - Laboratoire de Biochimie, CNRS UMR 6198, IFR 53 Biomolecules, Universite de 
      Reims-Champagne, Reims, France. william.hornebeck@univ-remis.fr
FAU - Bellon, G
AU  - Bellon G
FAU - Emonard, H
AU  - Emonard H
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20050122
PL  - France
TA  - Pathol Biol (Paris)
JT  - Pathologie-biologie
JID - 0265365
RN  - 0 (Fibronectins)
RN  - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
SB  - IM
MH  - Amino Acid Motifs
MH  - Fibronectins/*physiology
MH  - Humans
MH  - Kinetics
MH  - Matrix Metalloproteinase 2/*chemistry/*metabolism
MH  - Substrate Specificity
MH  - Tissue Inhibitor of Metalloproteinase-2/metabolism
RF  - 57
EDAT- 2005/08/09 09:00
MHDA- 2005/12/29 09:00
CRDT- 2005/08/09 09:00
PHST- 2004/11/26 00:00 [received]
PHST- 2004/12/07 00:00 [accepted]
PHST- 2005/08/09 09:00 [pubmed]
PHST- 2005/12/29 09:00 [medline]
PHST- 2005/08/09 09:00 [entrez]
AID - S0369-8114(04)00304-9 [pii]
AID - 10.1016/j.patbio.2004.12.015 [doi]
PST - ppublish
SO  - Pathol Biol (Paris). 2005 Sep;53(7):405-10. doi: 10.1016/j.patbio.2004.12.015. 
      Epub 2005 Jan 22.