PMID- 10525409 OWN - NLM STAT- MEDLINE DCOM- 19991104 LR - 20131121 IS - 0022-2836 (Print) IS - 0022-2836 (Linking) VI - 292 IP - 4 DP - 1999 Oct 1 TI - Structure of recombinant mouse collagenase-3 (MMP-13). PG - 837-44 AB - The matrix metalloproteinases are crucial in the physiological and pathological degradation of the mammalian extracellular matrix, including breast tumours, and osteoarthritic cartilage. These enzymes are classified according to their matrix substrate specificity. Collagenase-3 (MMP-13) is a member of this family and preferentially cleaves type II collagen, cartilage, fibronectin and aggrecan. Collagenase-3 is normally expressed in hypertrophic chondrocytes, periosteal cells, and osteoblasts during bone development. The structure of the catalytic domain of recombinant mouse collagenase-3, complexed to the hydroxamate inhibitor (RS-113456), is reported at 2.0 A resolution. Molecular replacement and weak phasing information from a single derivative determined the structure. Neither molecular replacement nor derivative methods had a sufficient radius of convergence to yield a refinable structure. The structure illuminates the atomic zinc ion interactions with functional groups in the active site, emphasizing zinc ligation and the very voluminous hydrophobic P1' group for the inhibitor potency. The structure provides insight into the specificity of this enzyme, facilitating design of specific inhibitors to target various diseases. FAU - Botos, I AU - Botos I AD - Department of Biochemistry and Biophysics, Texas A&M University, TX, 77843-2128, USA. FAU - Meyer, E AU - Meyer E FAU - Swanson, S M AU - Swanson SM FAU - Lemaitre, V AU - Lemaitre V FAU - Eeckhout, Y AU - Eeckhout Y FAU - Meyer, E F AU - Meyer EF LA - eng SI - PDB/1CXV SI - SWISSPROT/P23097 SI - SWISSPROT/P33435 SI - SWISSPROT/P45452 PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - J Mol Biol JT - Journal of molecular biology JID - 2985088R RN - 0 (Hydroxamic Acids) RN - 0 (Matrix Metalloproteinase Inhibitors) RN - 0 (Pyrans) RN - 0 (RS 113456) RN - 0 (Recombinant Proteins) RN - EC 3.4.24.- (Collagenases) RN - EC 3.4.24.- (MMP13 protein, human) RN - EC 3.4.24.- (Matrix Metalloproteinase 13) RN - EC 3.4.24.- (Matrix Metalloproteinases) RN - EC 3.4.24.- (Mmp13 protein, mouse) RN - J41CSQ7QDS (Zinc) RN - SY7Q814VUP (Calcium) SB - IM MH - Amino Acid Sequence MH - Animals MH - Binding Sites MH - Calcium/metabolism MH - *Catalytic Domain MH - Collagenases/*chemistry/*metabolism MH - Crystallization MH - Crystallography, X-Ray MH - Humans MH - Hydrogen Bonding MH - Hydroxamic Acids/chemistry/metabolism MH - Matrix Metalloproteinase 13 MH - Matrix Metalloproteinase Inhibitors MH - Matrix Metalloproteinases/*chemistry/*metabolism MH - Mice MH - Models, Molecular MH - Molecular Sequence Data MH - Protein Binding MH - Protein Conformation MH - Pyrans/chemistry/*metabolism MH - Recombinant Proteins/antagonists & inhibitors/chemistry/metabolism MH - Zinc/metabolism EDAT- 1999/10/20 00:00 MHDA- 1999/10/20 00:01 CRDT- 1999/10/20 00:00 PHST- 1999/10/20 00:00 [pubmed] PHST- 1999/10/20 00:01 [medline] PHST- 1999/10/20 00:00 [entrez] AID - 10.1006/jmbi.1999.3068 [doi] AID - S0022-2836(99)93068-1 [pii] PST - ppublish SO - J Mol Biol. 1999 Oct 1;292(4):837-44. doi: 10.1006/jmbi.1999.3068.