Sandbox Reserved 1125: Difference between revisions
From Proteopedia
Jump to navigationJump to search
Laura Dutto (talk | contribs) No edit summary |
Laura Dutto (talk | contribs) No edit summary |
||
| Line 63: | Line 63: | ||
== Mechanism == | == Mechanism == | ||
To express collagenolytic activity, MMP-8 needs to have both the catalytic and hemopexin domains but it is not clear how the hemopexin domain help to cleave triple-helical collagens because it does not bind to collagen.<ref>PMID:8489511</ref> Moreover, MMP-8 is secreted as inactive proproteins and then activated after a cleavage by extracellular proteinases. Indeed, it can't be activated without removal of the activation peptide. But recent evidences suggest that this protease activation is blocked by the formation of an intramolecular complex between the propeptide domain on the Cysteine residue (Cys91) and essential zinc atom in the catalytic domain. It is called the ''Cysteine-switch''. This discovery is unprecedented in enzymology and offers the opportunity for multiple modes of physiological activation of MMP-8. Moreover, since conditions in different cells and tissues may match those necessary to effect one of these activation modes for a given MMP, this may offer metabolic flexibility in the control of MMP activation.<ref>PMID:2164689</ref> | To express collagenolytic activity, MMP-8 needs to have both the catalytic and hemopexin domains but it is not clear how the hemopexin domain help to cleave triple-helical collagens because it does not bind to collagen.<ref>PMID:8489511</ref><ref>PMID:15257288</ref> Moreover, MMP-8 is secreted as inactive proproteins and then activated after a cleavage by extracellular proteinases. Indeed, it can't be activated without removal of the activation peptide. But recent evidences suggest that this protease activation is blocked by the formation of an intramolecular complex between the propeptide domain on the Cysteine residue (Cys91) and essential zinc atom in the catalytic domain. It is called the ''Cysteine-switch''. This discovery is unprecedented in enzymology and offers the opportunity for multiple modes of physiological activation of MMP-8. Moreover, since conditions in different cells and tissues may match those necessary to effect one of these activation modes for a given MMP, this may offer metabolic flexibility in the control of MMP activation.<ref>PMID:2164689</ref> | ||
To allow cleavage of the individual alpha chains of collagen, the binding of activated MMP-8 must partially unwind triple helix by inducing a conformational change in alpha chain. However, the molecular basis of this mechanism is not known.<ref>PMID:6270090</ref> | To allow cleavage of the individual alpha chains of collagen, the binding of activated MMP-8 must partially unwind triple helix by inducing a conformational change in alpha chain. However, the molecular basis of this mechanism is not known.<ref>PMID:6270090</ref> | ||
