Sandbox Reserved 468: Difference between revisions
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In the third mechanism, the Manzetti-mechanism, Manzetti Sergio and colleagues provided evidence that a coordination between water and zinc during catalysis was unlikely, and suggested a third mechanism wherein a histidine participates in catalysis by allowing the Zn2+ ion to assume a quasi-penta coordinated state, via its dissociation from it. In this state, the Zn2+ ion is coordinated with the two oxygen atoms from the catalytic glutamic acid, the substrate's carbonyl oxygen atom, and the two histidine residues, and can polarize the glutamic acid's oxygen atom, proximate the scissile bond, and induce it to act as reversible electron donor. This forms an oxyanion transition state. At this stage, a water molecule acts on the dissociated scissile bond and completes the hydrolyzation of the substrate [5][6]. | In the third mechanism, the Manzetti-mechanism, Manzetti Sergio and colleagues provided evidence that a coordination between water and zinc during catalysis was unlikely, and suggested a third mechanism wherein a histidine participates in catalysis by allowing the Zn2+ ion to assume a quasi-penta coordinated state, via its dissociation from it. In this state, the Zn2+ ion is coordinated with the two oxygen atoms from the catalytic glutamic acid, the substrate's carbonyl oxygen atom, and the two histidine residues, and can polarize the glutamic acid's oxygen atom, proximate the scissile bond, and induce it to act as reversible electron donor. This forms an oxyanion transition state. At this stage, a water molecule acts on the dissociated scissile bond and completes the hydrolyzation of the substrate [5][6]. | ||
'''Inhibition''' | |||
MMPs are inhibited by specific endogenous tissue inhibitor of metalloproteinases (TIMPs), which comprise a family of four protease inhibitors: TIMP-1, TIMP-2, TIMP-3, and TIMP-4. There are also synthetic inhibitors which generally work by binding the catalytic zinc atom at the MMP active site tightly. The common groups used for synthetic inhibition include hydroxamates, carboxylates, thiols, and phosphinyls. Hydroxymates are particularly potent inhibitors of MMPs and other zinc-dependent enzymes, due to their bidentate chelation of the zinc atom [5]. | |||
== Medical Implications == | == Medical Implications == | ||
