7WXX

Crystal structure of human MMP-7 in complex with inhibitor

Summary for 7WXX

• Entry DOI: 10.2210/pdb7wxx/pdb
• Descriptor: Matrilysin, Peptide Inhibitor, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: matrilysin, matrin, matrix metalloproteinase-7, pump-1 protease, uterine metalloproteinase, hydrolase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 20323.92

Authors

Kamitani, M.,Oka, Y.,Tabuse, H. (deposition date: 2022-02-15, release date: 2022-10-05, Last modification date: 2023-11-29)

Primary citation

Tabuse, H.,Abe-Sato, K.,Kanazawa, H.,Yashiro, M.,Tamura, Y.,Kamitani, M.,Hitaka, K.,Gunji, E.,Mitani, A.,Kojima, N.,Oka, Y.
Discovery of Highly Potent and Selective Matrix Metalloproteinase-7 Inhibitors by Hybridizing the S1' Subsite Binder with Short Peptides.
J.Med.Chem., 65:13253-13263, 2022

PubMed Abstract: Matrix metalloproteinase-7 (MMP-7) has emerged as a protein playing important roles in both physiological and pathophysiological processes. Despite the growing interest in MMP-7 as a potential therapeutic target for diseases including cancer and fibrosis, potent and selective MMP-7 inhibitors have yet to be identified. Compound , previously reported by Edman and co-workers, binds to the S1' subsite of MMP-7, exhibiting moderate inhibitory activity and selectivity. To achieve both higher inhibitory activity and selectivity, we conceived hybridizing with short peptides. The initially designed compound , which was a hybrid molecule between and a tripeptide (Ala-Leu-Met) derived from an MMP-2-inhibitory peptide (APP-IP), showed enhanced MMP-7-inhibitory activity. Subsequent optimization of the peptide moiety led to the development of compound with remarkable potency for MMP-7 and selectivity over other MMP subtypes.

PubMed: 36137271
DOI: 10.1021/acs.jmedchem.2c01088

Experimental method

X-RAY DIFFRACTION (1.5 Å)