Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T20401 | Target Info | |||
| Target Name | Carbonic anhydrase II (CA-II) | ||||
| Synonyms | Carbonic anhydrase C; Carbonic anhydrase 2; Carbonate dehydratase II; CAC | ||||
| Target Type | Successful Target | ||||
| Gene Name | CA2 | ||||
| Biochemical Class | Alpha-carbonic anhydrase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Acetazolamide | Ligand Info | |||
| Canonical SMILES | CC(=O)NC1=NN=C(S1)S(=O)(=O)N | ||||
| InChI | 1S/C4H6N4O3S2/c1-2(9)6-3-7-8-4(12-3)13(5,10)11/h1H3,(H2,5,10,11)(H,6,7,9) | ||||
| InChIKey | BZKPWHYZMXOIDC-UHFFFAOYSA-N | ||||
| PubChem Compound ID | 1986 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 6QEB Assessment of a large enzyme-drug complex by proton-detected solid-state NMR without deuteration | ||||||
| Method | Solid-state NMR | Resolution | N.A. | Mutation | No | [1] |
| PDB Sequence |
MSHHWGYGKH
10 NGPEHWHKDF20 PIAKGERQSP30 VDIDTHTAKY40 DPSLKPLSVS50 YDQATSLRIL 60 NNGHAFNVEF70 DDSQDKAVLK80 GGPLDGTYRL90 IQFHFHWGSL100 DGQGSEHTVD 110 KKKYAAELHL120 VHWNTKYGDF130 GKAVQQPDGL140 AVLGIFLKVG150 SAKPGLQKVV 160 DVLDSIKTKG170 KSADFTNFDP180 RGLLPESLDY190 WTYPGSLTTP200 PLLECVTWIV 210 LKEPISVSSE220 QVLKFRKLNF230 NGEGEPEELM240 VDNWRPAQPL250 KNRQIKASFK 260
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| PDB ID: 3HS4 Human carbonic anhydrase II complexed with acetazolamide | ||||||
| Method | X-ray diffraction | Resolution | 1.10 Å | Mutation | No | [2] |
| PDB Sequence |
HWGYGKHNGP
13 EHWHKDFPIA23 KGERQSPVDI33 DTHTAKYDPS43 LKPLSVSYDQ53 ATSLRILNNG 63 HAFNVEFDDS73 QDKAVLKGGP83 LDGTYRLIQF93 HFHWGSLDGQ103 GSEHTVDKKK 113 YAAELHLVHW123 NTKYGDFGKA134 VQQPDGLAVL144 GIFLKVGSAK154 PGLQKVVDVL 164 DSIKTKGKSA174 DFTNFDPRGL184 LPESLDYWTY194 PGSLTTPPLL204 ECVTWIVLKE 214 PISVSSEQVL224 KFRKLNFNGE234 GEPEELMVDN244 WRPAQPLKNR254 QIKASFK |
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HIS4
3.556
TRP5
3.491
GLY6
4.944
HIS10
4.415
ASN11
3.264
GLY12
4.487
HIS15
2.957
TRP16
3.567
LYS18
4.078
ASP19
2.730
PHE20
3.633
GLN92
3.097
HIS94
3.232
HIS96
3.272
GLU106
4.083
VAL109
3.771
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| PDB ID: 3V2M Effect of Sucrose and Glycerol as Cryoprotectans, on the Inhibition of Human Carbonic Anhydrase II | ||||||
| Method | X-ray diffraction | Resolution | 1.47 Å | Mutation | No | [3] |
| PDB Sequence |
HWGYGKHNGP
13 EHWHKDFPIA23 KGERQSPVDI33 DTHTAKYDPS43 LKPLSVSYDQ53 ATSLRILNNG 63 HAFNVEFDDS73 QDKAVLKGGP83 LDGTYRLIQF93 HFHWGSLDGQ103 GSEHTVDKKK 113 YAAELHLVHW123 NTKYGDFGKA134 VQQPDGLAVL144 GIFLKVGSAK154 PGLQKVVDVL 164 DSIKTKGKSA174 DFTNFDPRGL184 LPESLDYWTY194 PGSLTTPPLL204 ECVTWIVLKE 214 PISVSSEQVL224 KFRKLNFNGE234 GEPEELMVDN244 WRPAQPLKNR254 QIKASFK |
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| PDB ID: 3DC3 Use of Carbonic Anhydrase II, IX Active-Site Mimic, for the Purpose of Screening Inhibitors for Possible Anti-Cancer Properties | ||||||
| Method | X-ray diffraction | Resolution | 1.70 Å | Mutation | Yes | [4] |
| PDB Sequence |
HWGYGKHNGP
13 EHWHKDFPIA23 KGERQSPVDI33 DTHTAKYDPS43 LKPLSVSYDQ53 ATSLRILNNG 63 HSFQVEFDDS73 QDKAVLKGGP83 LDGTYRLIQF93 HFHWGSLDGQ103 GSEHTVDKKK 113 YAAELHLVHW123 NTKYGDFGKA134 VQQPDGLAVL144 GIFLKVGSAK154 PGLQKVVDVL 164 DSIKTKGKSA174 DFTNFDPRGL184 LPESLDYWTY194 PGSLTTPPLL204 ECVTWIVLKE 214 PISVSSEQVL224 KFRKLNFNGE234 GEPEELMVDN244 WRPAQPLKNR254 QIKASFK |
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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 .AZM or .AZM2 or .AZM3 or :3AZM;style chemicals stick;color identity;select .A:92 or .A:94 or .A:96 or .A:106 or .A:119 or .A:121 or .A:131 or .A:143 or .A:197 or .A:198 or .A:199 or .A:200 or .A:209; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| PDB ID: 3V2J Effect of Sucrose and Glycerol as Cryoprotectans, on the Inhibition of Human Carbonic Anhydrase II | ||||||
| Method | X-ray diffraction | Resolution | 1.70 Å | Mutation | No | [5] |
| PDB Sequence |
HWGYGKHNGP
13 EHWHKDFPIA23 KGERQSPVDI33 DTHTAKYDPS43 LKPLSVSYDQ53 ATSLRILNNG 63 HAFNVEFDDS73 QDKAVLKGGP83 LDGTYRLIQF93 HFHWGSLDGQ103 GSEHTVDKKK 113 YAAELHLVHW123 NTKYGDFGKA134 VQQPDGLAVL144 GIFLKVGSAK154 PGLQKVVDVL 164 DSIKTKGKSA174 DFTNFDPRGL184 LPESLDYWTY194 PGSLTTPPLL204 ECVTWIVLKE 214 PISVSSEQVL224 KFRKLNFNGE234 GEPEELMVDN244 WRPAQPLKNR254 QIKASFK |
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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 .AZM or .AZM2 or .AZM3 or :3AZM;style chemicals stick;color identity;select .A:91 or .A:92 or .A:94 or .A:96 or .A:106 or .A:119 or .A:121 or .A:131 or .A:143 or .A:197 or .A:198 or .A:199 or .A:200 or .A:202 or .A:207 or .A:209; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 6YMA MicroED structure of acetazolamide-bound human carbonic anhydrase II | ||||||
| Method | Electron crystallography | Resolution | 2.50 Å | Mutation | No | [6] |
| PDB Sequence |
HWGYGKHNGP
13 EHWHKDFPIA23 KGERQSPVDI33 DTHTAKYDPS43 LKPLSVSYDQ53 ATSLRILNNG 63 HAFNVEFDDS73 QDKAVLKGGP83 LDGTYRLIQF93 HFHWGSLDGQ103 GSEHTVDKKK 113 YAAELHLVHW123 NTKYGDFGKA134 VQQPDGLAVL144 GIFLKVGSAK154 PGLQKVVDVL 164 DSIKTKGKSA174 DFTNFDPRGL184 LPESLDYWTY194 PGSLTTPPLL204 ECVTWIVLKE 214 PISVSSEQVL224 KFRKLNFNGE234 GEPEELMVDN244 WRPAQPLKNR254 QIKASFK |
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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 .AZM or .AZM2 or .AZM3 or :3AZM;style chemicals stick;color identity;select .A:91 or .A:92 or .A:94 or .A:96 or .A:106 or .A:119 or .A:121 or .A:131 or .A:143 or .A:197 or .A:198 or .A:199 or .A:200 or .A:209; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 1YDB STRUCTURAL BASIS OF INHIBITOR AFFINITY TO VARIANTS OF HUMAN CARBONIC ANHYDRASE II | ||||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | No | [7] |
| PDB Sequence |
WGYGKHNGPE
14 HWHKDFPIAK24 GERQSPVDID34 THTAKYDPSL44 KPLSVSYDQA54 TSLRILNNGH 64 AFNVEFDDSQ74 DKAVLKGGPL84 DGTYRLIQFH94 FHWGSLDGQG104 SEHTVDKKKY 114 AAELHLVHWN124 TKYGDFGKAV135 QQPDGLAVLG145 IFLKVGSAKP155 GLQKVVDVLD 165 SIKTKGKSAD175 FTNFDPRGLL185 PESLDYWTYP195 GSFTTPPLLE205 CVTWIVLKEP 215 ISVSSEQVLK225 FRKLNFNGEG235 EPEELMVDNW245 RPAQPLKNRQ255 IKASF |
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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 .AZM or .AZM2 or .AZM3 or :3AZM;style chemicals stick;color identity;select .A:92 or .A:94 or .A:96 or .A:106 or .A:119 or .A:121 or .A:131 or .A:143 or .A:197 or .A:198 or .A:199 or .A:200 or .A:201 or .A:209; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 2H4N H94N CARBONIC ANHYDRASE II COMPLEXED WITH ACETAZOLAMIDE | ||||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | Yes | [8] |
| PDB Sequence |
HWGYGKHNGP
13 EHWHKDFPIA23 KGERQSPVDI33 DTHTAKYDPS43 LKPLSVSYDQ53 ATSLRILNNG 63 HAFNVEFDDS73 QDKAVLKGGP83 LDGTYRLIQF93 NFHWGSLDGQ103 GSEHTVDKKK 113 YAAELHLVHW123 NTKYGDFGKA134 VQQPDGLAVL144 GIFLKVGSAK154 PGLQKVVDVL 164 DSIKTKGKSA174 DFTNFDPRGL184 LPESLDYWTY194 PGSLTTPPLL204 ECVTWIVLKE 214 PISVSSEQVL224 KFRKLNFNGE234 GEPEELMVDN244 WRPAQPLKNR254 QIKASFK |
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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 .AZM or .AZM2 or .AZM3 or :3AZM;style chemicals stick;color identity;select .A:92 or .A:94 or .A:96 or .A:106 or .A:119 or .A:121 or .A:131 or .A:143 or .A:197 or .A:198 or .A:199 or .A:200 or .A:209; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 1ZSB CARBONIC ANHYDRASE II MUTANT E117Q, TRANSITION STATE ANALOGUE ACETAZOLAMIDE | ||||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | Yes | [9] |
| PDB Sequence |
HWGYGKHNGP
13 EHWHKDFPIA23 KGERQSPVDI33 DTHTAKYDPS43 LKPLSVSYDQ53 ATSLRILNNG 63 HAFNVEFDDS73 QDKAVLKGGP83 LDGTYRLIQF93 HFHWGSLDGQ103 GSEHTVDKKK 113 YAAQLHLVHW123 NTKYGDFGKA134 VQQPDGLAVL144 GIFLKVGSAK154 PGLQKVVDVL 164 DSIKTKGKSA174 DFTNFDPRGL184 LPESLDYWTY194 PGSLTTPPLL204 ECVTWIVLKE 214 PISVSSEQVL224 KFRKLNFNGE234 GEPEELMVDN244 WRPAQPLKNR254 QIKASFK |
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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 .AZM or .AZM2 or .AZM3 or :3AZM;style chemicals stick;color identity;select .A:91 or .A:92 or .A:94 or .A:96 or .A:106 or .A:119 or .A:121 or .A:131 or .A:143 or .A:197 or .A:198 or .A:199 or .A:200 or .A:209; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 1YDA STRUCTURAL BASIS OF INHIBITOR AFFINITY TO VARIANTS OF HUMAN CARBONIC ANHYDRASE II | ||||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [7] |
| PDB Sequence |
WGYGKHNGPE
14 HWHKDFPIAK24 GERQSPVDID34 THTAKYDPSL44 KPLSVSYDQA54 TSLRILNNGH 64 AFNVEFDDSQ74 DKAVLKGGPL84 DGTYRLIQFH94 FHWGSLDGQG104 SEHTVDKKKY 114 AAELHLVHWN124 TKYGDFGKAV135 QQPDGLAVLG145 IFLKVGSAKP155 GLQKVVDVLD 165 SIKTKGKSAD175 FTNFDPRGLL185 PESLDYWTYP195 GSETTPPLLE205 CVTWIVLKEP 215 ISVSSEQVLK225 FRKLNFNGEG235 EPEELMVDNW245 RPAQPLKNRQ255 IKASF |
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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 .AZM or .AZM2 or .AZM3 or :3AZM;style chemicals stick;color identity;select .A:92 or .A:94 or .A:96 or .A:106 or .A:119 or .A:121 or .A:131 or .A:143 or .A:197 or .A:198 or .A:199 or .A:200 or .A:207 or .A:209; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 1YDD STRUCTURAL BASIS OF INHIBITOR AFFINITY TO VARIANTS OF HUMAN CARBONIC ANHYDRASE II | ||||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [7] |
| PDB Sequence |
HWGYGKHNGP
13 EHWHKDFPIA23 KGERQSPVDI33 DTHTAKYDPS43 LKPLSVSYDQ53 ATSLRILNNG 63 HAFNVEFDDS73 QDKAVLKGGP83 LDGTYRLIQF93 HFHWGSLDGQ103 GSEHTVDKKK 113 YAAELHLVHW123 NTKYGDFGKA134 VQQPDGLAVL144 GIFLKVGSAK154 PGLQKVVDVL 164 DSIKTKGKSA174 DFTNFDPRGL184 LPESLDYWTY194 PGSRTTPPLL204 ECVTWIVLKE 214 PISVSSEQVL224 KFRKLNFNGE234 GEPEELMVDN244 WRPAQPLKNR254 QIKASF |
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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 .AZM or .AZM2 or .AZM3 or :3AZM;style chemicals stick;color identity;select .A:92 or .A:94 or .A:96 or .A:106 or .A:119 or .A:121 or .A:131 or .A:143 or .A:197 or .A:198 or .A:199 or .A:200 or .A:209; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 4K0S Structure of HCAIX mimic (HCAII with 5 mutations in active site) in complex with acetazolamide | ||||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | Yes | [10] |
| PDB Sequence |
HWGYGKHNGP
13 EHWHKDFPIA23 KGERQSPVDI33 DTHTAKYDPS43 LKPLSVSYDQ53 ATSLRILNNG 63 HSFQVTFDDS73 QDKAVLKGGP83 LDGTYRLIQF93 HFHWGSLDGQ103 GSEHTVDKKK 113 YAAELHLVHW123 NTKYGDLGKA134 VQQPDGLAVL144 GIFLKVGSAK154 PGLQKVVDVL 164 DSIKTEGKSA174 DFTNFDPRGL184 LPESLDYWTY194 PGSLTTPPLL204 ECVTWIVLKE 214 PISVSSEQVL224 KFRKLNFNGE234 GEPEELMVDN244 WRPAQPLKNR254 QIKASFK |
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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 .AZM or .AZM2 or .AZM3 or :3AZM;style chemicals stick;color identity;select .A:92 or .A:94 or .A:96 or .A:106 or .A:119 or .A:121 or .A:131 or .A:141 or .A:143 or .A:197 or .A:198 or .A:199 or .A:200 or .A:209; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 4G0C Neutron structure of acetazolamide-bound human carbonic anhydrase II reveal molecular details of drug binding. | ||||||
| Method | Neutron diffraction | Resolution | 2.00 Å | Mutation | No | [11] |
| PDB Sequence |
HWGYGKHNGP
13 EHWHKDFPIA23 KGERQSPVDI33 DTHTAKYDPS43 LKPLSVSYDQ53 ATSLRILNNG 63 HAFNVEFDDS73 QDKAVLKGGP83 LDGTYRLIQF93 HFHWGSLDGQ103 GSEHTVDKKK 113 YAAELHLVHW123 NTKYGDFGKA134 VQQPDGLAVL144 GIFLKVGSAK154 PGLQKVVDVL 164 DSIKTKGKSA174 DFTNFDPRGL184 LPESLDYWTY194 PGSLTTPPLL204 ECVTWIVLKE 214 PISVSSEQVL224 KFRKLNFNGE234 GEPEELMVDN244 WRPAQPLKNR254 QIKASFK |
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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 .AZM or .AZM2 or .AZM3 or :3AZM;style chemicals stick;color identity;select .A:91 or .A:92 or .A:94 or .A:96 or .A:106 or .A:119 or .A:121 or .A:131 or .A:135 or .A:141 or .A:143 or .A:197 or .A:198 or .A:199 or .A:200 or .A:202 or .A:207 or .A:209; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Assessment of a Large Enzyme-Drug Complex by Proton-Detected Solid-State NMR Spectroscopy without Deuteration. Angew Chem Int Ed Engl. 2019 Apr 16;58(17):5758-5762. | ||||
| REF 2 | High-resolution structure of human carbonic anhydrase II complexed with acetazolamide reveals insights into inhibitor drug design. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2009 Oct 1;65(Pt 10):992-5. | ||||
| REF 3 | Effect of Sucrose and Glycerol as Cryoprotectans, on the Inhibition of Human Carbonic Anhydrase II | ||||
| REF 4 | Design of a carbonic anhydrase IX active-site mimic to screen inhibitors for possible anticancer properties. Biochemistry. 2009 Feb 17;48(6):1322-31. | ||||
| REF 5 | Effect of Sucrose and Glycerol as Cryoprotectans, on the Inhibition of Human Carbonic Anhydrase II | ||||
| REF 6 | Visualizing drug binding interactions using microcrystal electron diffraction. Commun Biol. 2020 Jul 31;3(1):417. | ||||
| REF 7 | Structural basis of inhibitor affinity to variants of human carbonic anhydrase II. Biochemistry. 1995 Mar 28;34(12):3981-9. | ||||
| REF 8 | Histidine --> carboxamide ligand substitutions in the zinc binding site of carbonic anhydrase II alter metal coordination geometry but retain catalytic activity. Biochemistry. 1997 Dec 16;36(50):15780-91. | ||||
| REF 9 | Reversal of the hydrogen bond to zinc ligand histidine-119 dramatically diminishes catalysis and enhances metal equilibration kinetics in carbonic anhydrase II. Biochemistry. 1996 Mar 19;35(11):3439-46. | ||||
| REF 10 | Developing isoform specific inhibitors against hCAIX using CAIX mimic | ||||
| REF 11 | Neutron diffraction of acetazolamide-bound human carbonic anhydrase II reveals atomic details of drug binding. J Am Chem Soc. 2012 Sep 12;134(36):14726-9. | ||||
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