Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T03500 | Target Info | |||
| Target Name | Matrix metalloproteinase-12 (MMP-12) | ||||
| Synonyms | Macrophage metalloelastase; Macrophage elastase; MME; ME; HME | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | MMP12 | ||||
| Biochemical Class | Peptidase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Acetohydroxamic acid | Ligand Info | |||
| Canonical SMILES | CC(=O)NO | ||||
| InChI | 1S/C2H5NO2/c1-2(4)3-5/h5H,1H3,(H,3,4) | ||||
| InChIKey | RRUDCFGSUDOHDG-UHFFFAOYSA-N | ||||
| PubChem Compound ID | 1990 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 3BA0 Crystal structure of full-length human MMP-12 | ||||||
| Method | X-ray diffraction | Resolution | 3.00 Å | Mutation | Yes | [1] |
| PDB Sequence |
GPVWRKHYIT
115 YRINNYTPDM125 NREDVDYAIR135 KAFQVWSNVT145 PLKFSKINTG155 MADILVVFAR 165 GAHGDDHAFD175 GKGGILAHAF185 GPGSGIGGDA195 HFDEDEFWTT205 HSGGTNLFLT 215 AVHEIGHSLG225 LGHSSDPKAV235 MFPTYKYVDI245 NTFRLSADDI255 RGIQSLYGDP 265 KENQRLPNPD275 NSEPALCDPN285 LSFDAVTTVG295 NKIFFFKDRF305 FWLKVSERPK 315 TSVNLISSLW325 PTLPSGIEAA335 YEIEARNQVF345 LFKDDKYWLI355 SNLRPEPNYP 365 KSIHSFGFPN375 FVKKIDAAVF385 NPRFYRTYFF395 VDNQYWRYDE405 RRQMMDPGYP 415 KLITKNFQGI425 GPKIDAVFYS435 KNKYYYFFQG445 SNQFEYDFLL455 QRITKTLKSN 465 SWFGC
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| PDB ID: 1OS2 Ternary enzyme-product-inhibitor complexes of human MMP12 | ||||||
| Method | X-ray diffraction | Resolution | 2.15 Å | Mutation | Yes | [2] |
| PDB Sequence |
MMGPVWRKHY
113 ITYRINNYTP123 DMNREDVDYA133 IRKAFQVWSN143 VTPLKFSKIN153 TGMADILVVF 163 ARGAHGDDHA173 FDGKGGILAH183 AFGPGSGIGG193 DAHFDEDEFW203 TTHSGGTNLF 213 LTAVHEIGHS223 LGLGHSSDPK233 AVMFPTYKYV243 DINTFRLSAD253 DIRGIQSLYG 263 DPKEN
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| PDB ID: 1Y93 Crystal structure of the catalytic domain of human MMP12 complexed with acetohydroxamic acid at atomic resolution | ||||||
| Method | X-ray diffraction | Resolution | 1.03 Å | Mutation | Yes | [3] |
| PDB Sequence |
GPVWRKHYIT
115 YRINNYTPDM125 NREDVDYAIR135 KAFQVWSNVT145 PLKFSKINTG155 MADILVVFAR 165 GAHGDDHAFD175 GKGGILAHAF185 GPGSGIGGDA195 HFDEDEFWTT205 HSGGTNLFLT 215 AVHEIGHSLG225 LGHSSDPKAV235 MFPTYKYVDI245 NTFRLSADDI255 RGIQSLYG |
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| PDB ID: 3LJG Human MMP12 in complex with non-zinc chelating inhibitor | ||||||
| Method | X-ray diffraction | Resolution | 1.31 Å | Mutation | Yes | [4] |
| PDB Sequence |
MGPVWRKHYI
114 TYRINNYTPD124 MNREDVDYAI134 RKAFQVWSNV144 TPLKFSKINT154 GMADILVVFA 164 RGAHGDDHAF174 DGKGGILAHA184 FGPGSGIGGD194 AHFDEDEFWT204 THSGGTNLFL 214 TAVHEIGHSL224 GLGHSSDPKA234 VMFPTYKYVD244 INTFRLSADD254 IRGIQSLYG |
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Click to Show 3D Structure of This Binding Site
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| PDB ID: 2HU6 Crystal structure of human MMP-12 in complex with acetohydroxamic acid and a bicyclic inhibitor | ||||||
| Method | X-ray diffraction | Resolution | 1.32 Å | Mutation | Yes | [5] |
| PDB Sequence |
GPVWRKHYIT
115 YRINNYTPDM125 NREDVDYAIR135 KAFQVWSNVT145 PLKFSKINTG155 MADILVVFAR 165 GAHGDDHAFD175 GKGGILAHAF185 GPGSGIGGDA195 HFDEDEFWTT205 HSGGTNLFLT 215 AVHEIGHSLG225 LGHSSDPKAV235 MFPTYKYVDI245 NTFRLSADDI255 RGIQSLYG |
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .HAE or .HAE2 or .HAE3 or :3HAE;style chemicals stick;color identity;select .A:180 or .A:182 or .A:183 or .A:184 or .A:218 or .A:219 or .A:222 or .A:228; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 3LIK Human MMP12 in complex with non-zinc chelating inhibitor | ||||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | Yes | [4] |
| PDB Sequence |
MGPVWRKHYI
114 TYRINNYTPD124 MNREDVDYAI134 RKAFQVWSNV144 TPLKFSKINT154 GMADILVVFA 164 RGAHGDDHAF174 DGKGGILAHA184 FGPGSGIGGD194 AHFDEDEFWT204 THSGGTNLFL 214 TAVHEIGHSL224 GLGHSSDPKA234 VMFPTYKYVD244 INTFRLSADD254 IRGIQSLYG |
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .HAE or .HAE2 or .HAE3 or :3HAE;style chemicals stick;color identity;select .A:180 or .A:182 or .A:183 or .A:184 or .A:218 or .A:219 or .A:222 or .A:228 or .A:238; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 3LIL Human MMP12 in complex with non-zinc chelating inhibitor | ||||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | Yes | [4] |
| PDB Sequence |
MGPVWRKHYI
114 TYRINNYTPD124 MNREDVDYAI134 RKAFQVWSNV144 TPLKFSKINT154 GMADILVVFA 164 RGAHGDDHAF174 DGKGGILAHA184 FGPGSGIGGD194 AHFDEDEFWT204 THSGGTNLFL 214 TAVHEIGHSL224 GLGHSSDPKA234 VMFPTYKYVD244 INTFRLSADD254 IRGIQSLYG |
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .HAE or .HAE2 or .HAE3 or :3HAE;style chemicals stick;color identity;select .A:180 or .A:182 or .A:183 or .A:184 or .A:218 or .A:219 or .A:222 or .A:228 or .A:238; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 6RD0 Human MMP12 catalytic domain in complex with AP280 | ||||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | Yes | [6] |
| PDB Sequence |
MGPVWRKHYI
114 TYRINNYTPD124 MNREDVDYAI134 RKAFQVWSNV144 TPLKFSKINT154 GMADILVVFA 164 RGAHGDDHAF174 DGKGGILAHA184 FGPGSGIGGD194 AHFDEDEFWT204 THSGGTNLFL 214 TAVHEIGHSL224 GLGHSSDPKA234 VMFPTYKYVD244 INTFRLSADD254 IRGIQSLYG |
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .HAE or .HAE2 or .HAE3 or :3HAE;style chemicals stick;color identity;select .A:180 or .A:182 or .A:183 or .A:184 or .A:218 or .A:219 or .A:222 or .A:228 or .A:238; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 1UTT Crystal Structure of MMP-12 complexed to 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl-4-(4-ethoxy[1,1-biphenyl]-4-yl)-4-oxobutanoic acid | ||||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | No | [7] |
| PDB Sequence |
GPVWRKHYIT
115 YRINNYTPDM125 NREDVDYAIR135 KAFQVWSNVT145 PLKFSKINTG155 MADILVVFAR 165 GAHGDFHAFD175 GKGGILAHAF185 GPGSGIGGDA195 HFDEDEFWTT205 HSGGTNLFLT 215 AVHEIGHSLG225 LGHSSDPKAV235 MFPTYKYVDI245 NTFRLSADDI255 RGIQSLYGD |
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .HAE or .HAE2 or .HAE3 or :3HAE;style chemicals stick;color identity;select .A:180 or .A:182 or .A:183 or .A:184 or .A:218 or .A:219 or .A:222 or .A:228; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 6RLY Human MMP12 (catalytic domain) in complex with AP316 | ||||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | Yes | [6] |
| PDB Sequence |
MGPVWRKHYI
114 TYRINNYTPD124 MNREDVDYAI134 RKAFQVWSNV144 TPLKFSKINT154 GMADILVVFA 164 RGAHGDDHAF174 DGKGGILAHA184 FGPGSGIGGD194 AHFDEDEFWT204 THSGGTNLFL 214 TAVHEIGHSL224 GLGHSSDPKA234 VMFPTYKYVD244 INTFRLSADD254 IRGIQSLYG |
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .HAE or .HAE2 or .HAE3 or :3HAE;style chemicals stick;color identity;select .A:180 or .A:182 or .A:183 or .A:184 or .A:218 or .A:219 or .A:222 or .A:228 or .A:238; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 1UTZ Crystal Structure of MMP-12 complexed to (2R)-3-({[4-[(pyridin-4-yl)phenyl]-thien-2-yl}carboxamido)(phenyl)propanoic acid | ||||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [7] |
| PDB Sequence |
GPVWRKHYIT
115 YRINNYTPDM125 NREDVDYAIR135 KAFQVWSNVT145 PLKFSKINTG155 MADILVVFAR 165 GAHGDFHAFD175 GKGGILAHAF185 GPGSGIGGDA195 HFDEDEFWTT205 HSGGTNLFLT 215 AVHEIGHSLG225 LGHSSDPKAV235 MFPTYKYVDI245 NTFRLSADDI255 RGIQSLYGD |
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .HAE or .HAE2 or .HAE3 or :3HAE;style chemicals stick;color identity;select .A:180 or .A:182 or .A:183 or .A:184 or .A:218 or .A:219 or .A:222 or .A:228 or .A:238; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 3LKA Catalytic domain of human MMP-12 complexed with hydroxamic acid and paramethoxy-sulfonyl amide | ||||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | Yes | [8] |
| PDB Sequence |
GPVWRKHYIT
115 YRINNYTPDM125 NREDVDYAIR135 KAFQVWSNVT145 PLKFSKINTG155 MADILVVFAR 165 GAHGDDHAFD175 GKGGILAHAF185 GPGSGIGGDA195 HFDEDEFWTT205 HSGGTNLFLT 215 AVHEIGHSLG225 LGHSSDPKAV235 MFPTYKYVDI245 NTFRLSADDI255 RGIQSLYG |
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .HAE or .HAE2 or .HAE3 or :3HAE;style chemicals stick;color identity;select .A:180 or .A:182 or .A:183 or .A:218 or .A:219 or .A:222 or .A:228; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 5N5J Human MMP12 in complex with 3-(5-(1,2-dithiolan-3-yl)pentanamido)propane-1-sulfonate | ||||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | Yes | [9] |
| PDB Sequence |
GPVWRKHYIT
115 YRINNYTPDM125 NREDVDYAIR135 KAFQVWSNVT145 PLKFSKINTG155 MADILVVFAR 165 GAHGDDHAFD175 GKGGILAHAF185 GPGSGIGGDA195 HFDEDEFWTT205 HSGGTNLFLT 215 AVHEIGHSLG225 LGHSSDPKAV235 MFPTYKYVDI245 NTFRLSADDI255 RGIQSLYG |
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .HAE or .HAE2 or .HAE3 or :3HAE;style chemicals stick;color identity;select .A:180 or .A:182 or .A:183 or .A:184 or .A:218 or .A:219 or .A:222 or .A:228 or .A:238; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 5N5K Human catalytic MMP-12 in complex with 5-(1,2-dithiolan-3-yl)-N-(3-hydroxypropyl)pentanamide | ||||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | Yes | [9] |
| PDB Sequence |
VWRKHYITYR
117 INNYTPDMNR127 EDVDYAIRKA137 FQVWSNVTPL147 KFSKINTGMA157 DILVVFARGA 167 HGDDHAFDGK177 GGILAHAFGP187 GSGIGGDAHF197 DEDEFWTTHS207 GGTNLFLTAV 217 HEIGHSLGLG227 HSSDPKAVMF237 PTYKYVDINT247 FRLSADDIRG257 IQSLYG |
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .HAE or .HAE2 or .HAE3 or :3HAE;style chemicals stick;color identity;select .A:180 or .A:182 or .A:183 or .A:184 or .A:218 or .A:219 or .A:222 or .A:228 or .A:238; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Evidence of reciprocal reorientation of the catalytic and hemopexin-like domains of full-length MMP-12. J Am Chem Soc. 2008 Jun 4;130(22):7011-21. | ||||
| REF 2 | X-ray structures of binary and ternary enzyme-product-inhibitor complexes of matrix metalloproteinases. Angew Chem Int Ed Engl. 2003 Jun 16;42(23):2673-6. | ||||
| REF 3 | Conformational variability of matrix metalloproteinases: beyond a single 3D structure. Proc Natl Acad Sci U S A. 2005 Apr 12;102(15):5334-9. | ||||
| REF 4 | Insights from selective non-phosphinic inhibitors of MMP-12 tailored to fit with an S1' loop canonical conformation. J Biol Chem. 2010 Nov 12;285(46):35900-9. | ||||
| REF 5 | Synthesis of bicyclic molecular scaffolds (BTAa): an investigation towards new selective MMP-12 inhibitors. Bioorg Med Chem. 2006 Nov 15;14(22):7392-403. | ||||
| REF 6 | Exploration of zinc-binding groups for the design of inhibitors for the oxytocinase subfamily of M1 aminopeptidases. Bioorg Med Chem. 2019 Dec 15;27(24):115177. | ||||
| REF 7 | Crystal structures of novel non-peptidic, non-zinc chelating inhibitors bound to MMP-12. J Mol Biol. 2004 Aug 20;341(4):1063-76. | ||||
| REF 8 | Entropic contribution to the linking coefficient in fragment based drug design: a case study. J Med Chem. 2010 May 27;53(10):4285-9. | ||||
| REF 9 | Lipoyl-Homotaurine Derivative (ADM_12) Reverts Oxaliplatin-Induced Neuropathy and Reduces Cancer Cells Malignancy by Inhibiting Carbonic Anhydrase IX (CAIX). J Med Chem. 2017 Nov 9;60(21):9003-9011. | ||||
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