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MARIO A. GARCÍA Y COLS. AN. R. ACAD. NAC. FARM.

(Glu198 in MMP-8) and coordinated to the Zn2+ ion. The water
donates a proton to the Glu residue that transfers it to the nitrogen
of the scissile amide. This is followed by the Glu residue shuttling
the remaining proton from the water molecule to the nitrogen of the
scissile amide with resultant peptide bond cleavage. During this
process, the positively charged Zn2+ ion helps to stabilize negative
charge at the carbon of the scissile amide and a conserved Ala
(Ala161 in MMP-8) residue helps to stabilize the positive charge at
the nitrogen of the scissile amide.

FIGURE 1. Mechanism of proteolysis carried out by MMPs, as reported by
Lovejoy et al.

Biological Implications of MMPs

Matrix metalloproteinases are responsible of remodelling and
degrading extracellular matrix, and are implicated in a wide variety
of biological processes such as embryonic development, blastocyst
implantation, nerve growth, ovulation, morphogenesis, angiogenesis,
tissue resorption and remodelling, bone remodelling, apoptosis,
cancer invasion and metastasis, arthritis (osteo- and rheumatoid-),
atherosclerotic plaque rupturing, pulmonary emphysema, aortic
aneurysms, breakdown of blood-brain barrier, periodontal disease,
skin ulceration, corneal ulceration, gastric ulcer, multiple sclerosis,
Crohn’s disease, psoriasis, dermatitis, congestive heart failure and
Alzheimer’s disease (9).

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