Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.24.17 (
MMP-3
)
3,419
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Matrix metalloproteinase 1
(
MMP-1
) cleaves types I, II, and III collagen triple helices into (3/4) and (1/4) fragments. To understand the structural elements responsible for this activity, various lengths of
MMP-1
segments have been introduced into
MMP-3
(
stromelysin 1
) starting from the C-terminal end.
MMP-3
/
MMP-1
chimeras and variants were overexpressed in Escherichia coli, folded from inclusion bodies, and isolated as zymogens. After activation, recombinant chimeras were tested for their ability to digest triple helical type I collagen at 25 degrees C. The results indicate that the nine residues (183)RWTNNFREY(191) located between the fifth beta-strand and the second alpha-helix in the catalytic domain of
MMP-1
are critical for the expression of collagenolytic activity. Mutation of Tyr(191) of
MMP-1
to Thr, the corresponding residue in
MMP-3
, reduced collagenolytic activity about 5-fold. Replacement of the nine residues with those of the
MMP-3
sequence further decreased the activity 2-fold. Those variants exhibited significant changes in substrate specificity and activity against gelatin and synthetic substrates, further supporting the notion that this region plays a critical role in the expression of collagenolytic activity. However, introduction of this sequence into
MMP-3
or a chimera consisting of the catalytic domain of
MMP-3
with the hinge region and the C-terminal hemopexin domain of
MMP-1
did not express any collagenolytic activity. It is therefore concluded that RWTNNFREY, together with the C-terminal hemopexin domain, is essential for collagenolytic activity but that additional structural elements in the catalytic domain are also required. These elements probably act in a concerted manner to cleave the collagen triple helix.
...
PMID:Identification of the (183)RWTNNFREY(191) region as a critical segment of matrix metalloproteinase 1 for the expression of collagenolytic activity. 1087 19
