FIGURE 3.

Structural comparison with mammalian pro-MMPs. A, schematic depicting of the structure of pro-MMP-2 (PDB 1EAK (89); MMP-2 residues in italics with superscripted numbering), shown only for its CD (Tyr¹¹⁰-Asp⁵² in cyan; the fibronectin type-II domains spanning Gln²¹⁹-Asp⁹² have been omitted, the black arrows pinpoint the insertion points) and prodomain (Pro⁴³-Asn¹⁰⁹ in pink, without the first 11 residues in extended conformation). The orientation displayed corresponds to that of Fig. 2A after applying a horizontal rotation of 15°. Residues of the conserved motif (Pro¹⁰⁰-Asp¹⁰⁶) key for structural integrity of the inhibitory segment are depicted for their side chains. B, close-up of A after removal of prodomain segment Pro⁴³-Asn⁶⁶ to provide insight into the interactions of the conserved motif. Key electrostatic interactions are shown as green lines. The catalytic glutamate, Glu⁴⁰⁴, is replaced by a glutamine, the histidines from the CSBZ are His⁴⁰³, His⁴⁰⁷, and His⁴¹³. C and D, scheme depicting the interaction modi of the propeptides of pro-MMP-2 through a cysteine-switch mechanism (C) and pKly18 through an aspartate-switch mechanism (D). The catalytic zinc ions are shown as magenta spheres and relevant interactions are shown as yellow dashed lines.