Fig. 25.14 Crystal structure of Ro 31-4724 (25.35, IC50 = 9 nM) and collagenase; the binding mode is shown. The hydroxamic acid binds in a bidentate-like manner to the zinc ion. Both amide groups form hydrogen bonds to the enzyme. The leucine side chain of the inhibitor in the P1′ position fills the S1′ pocket, which is oriented toward the protein’s interior. The alanine methyl group binds in the S3′ pocket, whereas the leucine side chain in position P2′ protrudes into the solvent because the S2′ pocket is practically non-existent.