Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T97008 | Target Info | |||
| Target Name | S-adenosylmethionine synthase type-2 (MAT2A) | ||||
| Synonyms | Methionine adenosyltransferase II; Methionine adenosyltransferase 2; MAT-II; MAT 2; AdoMet synthase 2 | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | MAT2A | ||||
| Biochemical Class | AdoMet synthase family | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Adenosine | Ligand Info | |||
| Canonical SMILES | C1=NC(=C2C(=N1)N(C=N2)C3C(C(C(O3)CO)O)O)N | ||||
| InChI | 1S/C10H13N5O4/c11-8-5-9(13-2-12-8)15(3-14-5)10-7(18)6(17)4(1-16)19-10/h2-4,6-7,10,16-18H,1H2,(H2,11,12,13)/t4-,6-,7-,10-/m1/s1 | ||||
| InChIKey | OIRDTQYFTABQOQ-KQYNXXCUSA-N | ||||
| PubChem Compound ID | 60961 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 5A1I The structure of Human MAT2A in complex with SAM, Adenosine, Methionine and PPNP. | ||||||
| Method | X-ray diffraction | Resolution | 1.09 Å | Mutation | No | [1] |
| PDB Sequence |
EGTFLFTSES
24 VGEGHPDKIC34 DQISDAVLDA44 HLQQDPDAKV54 ACETVAKTGM64 ILLAGEITSR 74 AAVDYQKVVR84 EAVKHIGYDD94 SSKGFDYKTC104 NVLVALEQQS114 PDIAQGVHLD 124 RNEEDIGAGD134 QGLMFGYATD144 ETEECMPLTI154 VLAHKLNAKL164 AELRRNGTLP 174 WLRPDSKTQV184 TVQYMQDRGA194 VLPIRVHTIV204 ISVQHDEEVC214 LDEMRDALKE 224 KVIKAVVPAK234 YLDEDTIYHL244 QPSGRFVIGG254 PQGDAGLTGR264 KIIVDTYGGW 274 GAHGGGAFSG284 KDYTKVDRSA294 AYAARWVAKS304 LVKGGLCRRV314 LVQVSYAIGV 324 SHPLSISIFH334 YGTSQKSERE344 LLEIVKKNFD354 LRPGVIVRDL364 DLKKPIYQRT 374 AAYGHFGRDS384 FPWEVPKKLK394 Y
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| PDB ID: 6FCD Human Methionine Adenosyltransferase II mutant (R264A) | ||||||
| Method | X-ray diffraction | Resolution | 1.70 Å | Mutation | Yes | [2] |
| PDB Sequence |
GTFLFTSESV
25 GEGHPDKICD35 QISDAVLDAH45 LQQDPDAKVA55 CETVAKTGMI65 LLAGEITSRA 75 AVDYQKVVRE85 AVKHIGYDDS95 SKGFDYKTCN105 VLVALEQQSP115 DIAQGVHLDR 125 NEEDIGAGDQ135 GLMFGYATDE145 TEECMPLTIV155 LAHKLNAKLA165 ELRRNGTLPW 175 LRPDSKTQVT185 VQYMQDRGAV195 LPIRVHTIVI205 SVQHDEEVCL215 DEMRDALKEK 225 VIKAVVPAKY235 LDEDTIYHLQ245 PSGRFVIGGP255 QGDAGLTGAK265 IIVDTYGGWG 275 AHGGGAFSGK285 DYTKVDRSAA295 YAARWVAKSL305 VKGGLCRRVL315 VQVSYAIGVS 325 HPLSISIFHY335 GTSQKSEREL345 LEIVKKNFDL355 RPGVIVRDLD365 LKKPIYQRTA 375 AYGHFGRDSF385 PWEVPKKLKY395
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| PDB ID: 6FBO Human Methionine Adenosyltransferase II mutant (S114A) in I222 crystal form | ||||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | Yes | [2] |
| PDB Sequence |
EGTFLFTSES
24 VGEGHPDKIC34 DQISDAVLDA44 HLQQDPDAKV54 ACETVAKTGM64 ILLAGEITSR 74 AAVDYQKVVR84 EAVKHIGYDD94 SSKGFDYKTC104 NVLVALEQQA114 PDIAQGVHLD 124 RNEEDIGAGD134 QGLMFGYATD144 ETEECMPLTI154 VLAHKLNAKL164 AELRRNGTLP 174 WLRPDSKTQV184 TVQYMQDRGA194 VLPIRVHTIV204 ISVQHDEEVC214 LDEMRDALKE 224 KVIKAVVPAK234 YLDEDTIYHL244 QPSGRFVIGG254 PQGDAGLTGR264 KIIVDTYGGW 274 GAHGGGAFSG284 KDYTKVDRSA294 AYAARWVAKS304 LVKGGLCRRV314 LVQVSYAIGV 324 SHPLSISIFH334 YGTSQKSERE344 LLEIVKKNFD354 LRPGVIVRDL364 DLKKPIYQRT 374 AAYGHFGRDS384 FPWEVPKKLK394 Y
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| PDB ID: 4KTV Structural insights of MAT enzymes: MATa2b complexed with adenosine and pyrophosphate | ||||||
| Method | X-ray diffraction | Resolution | 3.30 Å | Mutation | No | [3] |
| PDB Sequence |
EGTFLFTSES
24 VGEGHPDKIC34 DQISDAVLDA44 HLQQDPDAKV54 ACETVAKTGM64 ILLAGEITSR 74 AAVDYQKVVR84 EAVKHIGYDD94 SSKGFDYKTC104 NVLVALEQQS114 PQGLMFGYAT 143 DETEECMPLT153 IVLAHKLNAK163 LAELRRNGTL173 PWLRPDSKTQ183 VTVQYMQDRG 193 AVLPIRVHTI203 VISVQHDEEV213 CLDEMRDALK223 EKVIKAVVPA233 KYLDEDTIYH 243 LQPSGRFVIG253 GPQGDAGLTG263 RKIIVDTYGG273 WGAHGGGAFS283 GKDYTKVDRS 293 AAYAARWVAK303 SLVKGGLCRR313 VLVQVSYAIG323 VSHPLSISIF333 HYGTSQKSER 343 ELLEIVKKNF353 DLRPGVIVRD363 LDLKKPIYQR373 TAAYGHFGRD383 SFPWEVPKKL 393 KY
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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 .ADN or .ADN2 or .ADN3 or :3ADN;style chemicals stick;color identity;select .A:29 or .A:30 or .A:179 or .A:180 or .A:181 or .A:206 or .A:247 or .A:249 or .A:250 or .A:252 or .A:253 or .A:258; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| PDB ID: 8AXZ Crystal structure of human methionine adenosyltransferase 2A (MAT2A) in complex with S-adenosylmethionine, adenosin and diphosphono-aminophosphonic acid. | ||||||
| Method | X-ray diffraction | Resolution | 1.15 Å | Mutation | No | [4] |
| PDB Sequence |
TFLFTSESVG
26 EGHPDKICDQ36 ISDAVLDAHL46 QQDPDAKVAC56 ETVAKTGMIL66 LAGEITSRAA 76 VDYQKVVREA86 VKHIGYDDSS96 KGFDYKTCNV106 LVALEQQSPD116 IAQGVHLDRN 126 EEDIGAGDQG136 LMFGYATDET146 EECMPLTIVL156 AHKLNAKLAE166 LRRNGTLPWL 176 RPDSKTQVTV186 QYMQDRGAVL196 PIRVHTIVIS206 VQHDEEVCLD216 EMRDALKEKV 226 IKAVVPAKYL236 DEDTIYHLQP246 SGRFVIGGPQ256 GDAGLTGRKI266 IVDTYGGWGA 276 HGGGAFSGKD286 YTKVDRSAAY296 AARWVAKSLV306 KGGLCRRVLV316 QVSYAIGVSH 326 PLSISIFHYG336 TSQKSERELL346 EIVKKNFDLR356 PGVIVRDLDL366 KKPIYQRTAA 376 YGHFGRDSFP386 WEVPKKLKY
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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 .ADN or .ADN2 or .ADN3 or :3ADN;style chemicals stick;color identity;select .A:29 or .A:30 or .A:179 or .A:180 or .A:181 or .A:206 or .A:247 or .A:249 or .A:250 or .A:252 or .A:257 or .A:258; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 6P9V Crystal Structure of hMAT Mutant K289L | ||||||
| Method | X-ray diffraction | Resolution | 2.05 Å | Mutation | Yes | [5] |
| PDB Sequence |
GTFLFTSESV
25 GEGHPDKICD35 QISDAVLDAH45 LQQDPDAKVA55 CETVAKTGMI65 LLAGEITSRA 75 AVDYQKVVRE85 AVKHIGYDDS95 SKGFDYKTCN105 VLVALEQQSP115 DIAQGVHLDR 125 NEEDIGAGDQ135 GLMFGYATDE145 TEECMPLTIV155 LAHKLNAKLA165 ELRRNGTLPW 175 LRPDSKTQVT185 VQYMQDRGAV195 LPIRVHTIVI205 SVQHDEEVCL215 DEMRDALKEK 225 VIKAVVPAKY235 LDEDTIYHLQ245 PSGRFVIGGP255 QGDAGLTGRK265 IIVDTYGGWG 275 AHGGGAFSGK285 DYTLVDRSAA295 YAARWVAKSL305 VKGGLCRRVL315 VQVSYAIGVS 325 HPLSISIFHY335 GTSQKSEREL345 LEIVKKNFDL355 RPGVIVRDLD365 LKKPIYQRTA 375 AYGHFGRDSF385 PWEVPKKLKY395
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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 .ADN or .ADN2 or .ADN3 or :3ADN;style chemicals stick;color identity;select .A:29 or .A:30 or .A:179 or .A:180 or .A:181 or .A:206 or .A:245 or .A:246 or .A:247 or .A:249 or .A:250 or .A:251 or .A:252 or .A:253 or .A:254 or .A:257 or .A:258; 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 | Crystallography captures catalytic steps in human methionine adenosyltransferase enzymes. Proc Natl Acad Sci U S A. 2016 Feb 23;113(8):2104-9. | ||||
| REF 2 | Control and regulation of S-Adenosylmethionine biosynthesis by the regulatory beta subunit and quinolone-based compounds. FEBS J. 2019 Jun;286(11):2135-2154. | ||||
| REF 3 | Structure and function study of the complex that synthesizes S-adenosylmethionine. IUCrJ. 2014 Jun 12;1(Pt 4):240-9. | ||||
| REF 4 | Crystal structure of human methionine adenosyltransferase 2A (MAT2A) in complex with S-adenosylmethionine, adenosin and diphosphono-aminophosphonic acid. | ||||
| REF 5 | Methionine Adenosyltransferase Engineering to Enable Bioorthogonal Platforms for AdoMet-Utilizing Enzymes. ACS Chem Biol. 2020 Mar 20;15(3):695-705. | ||||
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