Fig 1: Metabolites showing positive and/or negative interaction with MMP-1,8,13. Metabolites showing positive interactions- with MMP1: octadecanoic acid, D-pinitol, gly-pro, palmitic a, N-methylglutamic a, hexadecanol, with MMP8: melibiose, citramalic a, gulose, pentadecanoic a, xylitol, tyrosine, epsilon-caprolactam, glucaric a, methyl-β-D-galactopyranoside, trans-ferulic a, ribose, tyramine, with MMP13: tartaric a., 2,4-bishydroxybutanoic a., galactonic a., tryptophane, glyceric a, malonic a, maleic a, ribonic a, β-alanine, 3-hydroxy-3-methylglutaric a, myo-inositol, ferulic a, 2-hydroxyglutaric a, N-acetyl-D-mannosamine, raffinose, succinic a, monomethylphosphate, alanine, L-(+) lactic a, with MMP1-8: none, with MMP1-13: none, with MMP8-13: 2,3-Dihydroxybutanedioic a, 2,4,6-tri-tert.-butylbenzenethiol, cis-aconitic a, citric a, digalactosylglycerol, DL-3,4-dihydroxyphenylglycol, fumaric a, galactinol, gentiobiose, glycerol, L-alanine, L-proline, myo-inositol-1-phosphate, threonic a, ursolic a, with MMP1-8-13: 2-O-glycerol-β-D-galactopyranoside, benzyl thiocyanate, hydroxylamine Metabolites showing negative interactions- with MMP1: 1-ethylglucopyranoside, 4-isopropylbenzoic a, α-D-glc-(1,2)- β-D-Fru, α-tocopherol, cis-aconitic a, D-allose, DL-3,4-dihydroxyphenyl glycol, gluconic acid lactone, L-norleucine, L-serine, L-threonine, malic a, maltotriose, melibiose, p-cymene, pyruvic a, raffinose, sucrose, trehalose, with MMP8: capric a, D-threitol, glutaric acid, glycine, mannitol, octadecanoic a, phosphoric a, salicylic acid glucopyranoside, squalene, with MMP13: 2-ketoisocaproic acid galactosylglycerol, myristic a, oleic a, porphine, with MMP1-8: 1-monooctadecanoylglycerol, kaempferol, lactic a, triacontanoic a, with MMP1-13: D-sphingosine, monomethylphosphate, oxalic a, shikimic a, xylitol, with MMP8-13: 2-hydroxypyridine, 2-pyrrolidinone, 2,4,6-tri-tert.-butylbenzenethiol, 4-aminobutyric a., 4-hydroxy-3-methoxybenzoic a., 4-hydroxybenzoic a, allo-inositol, α-ketoglutaric a, arachidic a, benzoic a, β-sitosterol, citraconic a, D-mannitol, D-pinitol, docosanol, dodecanoic a, dotriacontanol, eicosanoic a, eicosanol, ethanolamine, glucopyranose, hesperetin, hexacosanol, hexadecanoic a, hydroquinone, L-alanine, L-proline, O-acetylsalicylic a, palatinitol, palmitic a, phytol, piceatannol, threitol, triacontanol, urea, vanillin, with MMP1-8-13: 1-benzylglucopyranoside, 1,3-bisethynylbenzene, 3,4-dihydroxybenzoic a, 4-trans-caffeoylquinic a, 5-trans-caffeoylquinic a, allose, behenic a, chlorogenic a, fructose, octacosanol, pipecolic a, proline, pyroglutamic a, quinic a, stearic a, tetracosanol, valine, octadecanol.
Fig 2: Molecular docking interactions of 7g (green sticks) into (A, B) MMP-10 active site (PDB ID: 1Q3A117) and (C, D) MMP-13 active site (PDB ID: 1XUD118). Molecular surfaces of the catalytic domains (grey) of (E) MMP-10 and (F) MMP-13 showing S1’ subunit (red), active site Zn2+ (light blue ball), zinc-chelating histidine residues (orange) and the docked 7g (green sticks). Binding interactions of the reference co-crystallized inhibitors are illustrated in the Supplementary Data (Figures S89 and S96).
Fig 3: (A) RMSD, (B) RMSF, (C) rGyr, and (D) hydrogen bonding of 7g-MMP-13 (PDB ID: 1XUD118) complex (mod III) during 50 ns MDs simulation. Results of MDs simulations of other mods are illustrated in the Supplementary Data.
Fig 4: The center-of-mass distance (COM) of (A) 7g-MMP-10 (PDB ID: 1Q3A117) (mod I) and (B) 7g-MMP-13 (PDB ID: 1XUD118) (mod III) complexes during 50 ns MDs simulation.
Fig 5: Contact frequency (CF) analysis of (A) 7g-MMP-10 (PDB ID: 1Q3A117) (mod I) and (B) 7g-MMP-13 (PDB ID: 1XUD118) (mod III) complexes during 50 ns MDs simulation.
Supplier Page from Abcam for MMP13 Inhibitor Screening Assay Kit (Colorimetric)