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| | <StructureSection load='1gx3' size='340' side='right'caption='[[1gx3]], [[Resolution|resolution]] 1.70Å' scene=''> | | <StructureSection load='1gx3' size='340' side='right'caption='[[1gx3]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1gx3]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GX3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1GX3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1gx3]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycolicibacterium_smegmatis Mycolicibacterium smegmatis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GX3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1GX3 FirstGlance]. <br> |
| - | </td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Arylamine_N-acetyltransferase Arylamine N-acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.5 2.3.1.5] </span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1gx3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gx3 OCA], [http://pdbe.org/1gx3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1gx3 RCSB], [http://www.ebi.ac.uk/pdbsum/1gx3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1gx3 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1gx3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gx3 OCA], [https://pdbe.org/1gx3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1gx3 RCSB], [https://www.ebi.ac.uk/pdbsum/1gx3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1gx3 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/NAT_MYCSM NAT_MYCSM] Catalyzes the transfer of the acetyl group from acetyl coenzyme A to the free amino group of arylamines and hydrazines. Substrates include isoniazid, anisidine, and 4-aminoveratrole, and to a much lesser extent, p-aminobenzoic acid.<ref>PMID:12054803</ref> <ref>PMID:9973365</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Arylamine N-acetyltransferase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Kawamura, A]] | + | [[Category: Mycolicibacterium smegmatis]] |
| - | [[Category: Mushtaq, A]] | + | [[Category: Kawamura A]] |
| - | [[Category: Noble, M]] | + | [[Category: Mushtaq A]] |
| - | [[Category: Sandy, J]] | + | [[Category: Noble M]] |
| - | [[Category: Sim, E]] | + | [[Category: Sandy J]] |
| - | [[Category: Sinclair, J]] | + | [[Category: Sim E]] |
| - | [[Category: Arylamine n- acetyltransferase]]
| + | [[Category: Sinclair J]] |
| - | [[Category: Drug metabolism]]
| + | |
| - | [[Category: Isoniazid]]
| + | |
| - | [[Category: Mycobacteria]]
| + | |
| - | [[Category: Nat]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
NAT_MYCSM Catalyzes the transfer of the acetyl group from acetyl coenzyme A to the free amino group of arylamines and hydrazines. Substrates include isoniazid, anisidine, and 4-aminoveratrole, and to a much lesser extent, p-aminobenzoic acid.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Arylamine N-acetyltransferases which acetylate and inactivate isoniazid, an anti-tubercular drug, are found in mycobacteria including Mycobacterium smegmatis and Mycobacterium tuberculosis. We have solved the structure of arylamine N-acetyltransferase from M. smegmatis at a resolution of 1.7 A as a model for the highly homologous NAT from M. tuberculosis. The fold closely resembles that of NAT from Salmonella typhimurium, with a common catalytic triad and domain structure that is similar to certain cysteine proteases. The detailed geometry of the catalytic triad is typical of enzymes which use primary alcohols or thiols as activated nucleophiles. Thermal mobility and structural variations identify parts of NAT which might undergo conformational changes during catalysis. Sequence conservation among eubacterial NATs is restricted to structural residues of the protein core, as well as the active site and a hinge that connects the first two domains of the NAT structure. The structure of M. smegmatis NAT provides a template for modelling the structure of the M. tuberculosis enzyme and for structure-based ligand design as an approach to designing anti-TB drugs.
The structure of arylamine N-acetyltransferase from Mycobacterium smegmatis--an enzyme which inactivates the anti-tubercular drug, isoniazid.,Sandy J, Mushtaq A, Kawamura A, Sinclair J, Sim E, Noble M J Mol Biol. 2002 May 10;318(4):1071-83. PMID:12054803[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sandy J, Mushtaq A, Kawamura A, Sinclair J, Sim E, Noble M. The structure of arylamine N-acetyltransferase from Mycobacterium smegmatis--an enzyme which inactivates the anti-tubercular drug, isoniazid. J Mol Biol. 2002 May 10;318(4):1071-83. PMID:12054803 doi:10.1016/S0022-2836(02)00141-9
- ↑ Payton M, Auty R, Delgoda R, Everett M, Sim E. Cloning and characterization of arylamine N-acetyltransferase genes from Mycobacterium smegmatis and Mycobacterium tuberculosis: increased expression results in isoniazid resistance. J Bacteriol. 1999 Feb;181(4):1343-7. PMID:9973365 doi:10.1128/JB.181.4.1343-1347.1999
- ↑ Sandy J, Mushtaq A, Kawamura A, Sinclair J, Sim E, Noble M. The structure of arylamine N-acetyltransferase from Mycobacterium smegmatis--an enzyme which inactivates the anti-tubercular drug, isoniazid. J Mol Biol. 2002 May 10;318(4):1071-83. PMID:12054803 doi:10.1016/S0022-2836(02)00141-9
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