MMP-TIMP interaction depends on residue 2 in TIMP-4.
Extracellular matrix remodeling and degradation are of great importance in both physiological and pathological situations. Matrix metalloproteinases (MMPs) and their natural occurring inhibitors - tissue inhibitors of metalloproteinases (TIMPs) - are involved in matrix turnover. Among the TIMPs there is only little specificity for inhibiting individual MMPs. In this report we describe the mutational analysis of the interaction of human TIMP-4 with several MMPs. The effects of different substitutions of residue 2 (Ser(2)) in the inhibitory domain of TIMP-4 were determined by kinetic measurements. Size, charge and polarity of residue 2 in the TIMP structure are key factors in MMP inhibition.
Stratmann
B
B
University of Bielefeld, Faculty of Chemistry, Biochemistry I, Universitätsstrasse 25, D-33615, Bielefeld, Germany.
Farr
M
M
Tschesche
H
H
D019943:Amino Acid Substitution; D006801:Humans; D007700:Kinetics; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D010843:Pichia / Q000235:genetics; D012694:Serine; D013329:Structure-Activity Relationship; D019714:Tissue Inhibitor of Metalloproteinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D000097792:Tissue Inhibitor of Metalloproteinase-4
D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9; D020782:Matrix Metalloproteinases; D012694:Serine; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4