|
|
| Line 3: |
Line 3: |
| | <StructureSection load='1w5r' size='340' side='right'caption='[[1w5r]], [[Resolution|resolution]] 1.45Å' scene=''> | | <StructureSection load='1w5r' size='340' side='right'caption='[[1w5r]], [[Resolution|resolution]] 1.45Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1w5r]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_smegmatis"_trevisan_1889 "bacillus smegmatis" trevisan 1889]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W5R OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1W5R FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1w5r]] is a 2 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=1W5R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1W5R FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1gx3|1gx3]]</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]] 1.45Å</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>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1w5r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w5r OCA], [https://pdbe.org/1w5r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1w5r RCSB], [https://www.ebi.ac.uk/pdbsum/1w5r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1w5r ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1w5r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w5r OCA], [http://pdbe.org/1w5r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1w5r RCSB], [http://www.ebi.ac.uk/pdbsum/1w5r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1w5r 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]] |
| Line 34: |
Line 35: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacillus smegmatis trevisan 1889]] | |
| - | [[Category: Arylamine N-acetyltransferase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bhakta, S]] | + | [[Category: Mycolicibacterium smegmatis]] |
| - | [[Category: Dupret, J M]] | + | [[Category: Bhakta S]] |
| - | [[Category: Holton, S J]] | + | [[Category: Dupret J-M]] |
| - | [[Category: Noble, M E.M]] | + | [[Category: Holton SJ]] |
| - | [[Category: Rodrigues-Lima, F]] | + | [[Category: Noble MEM]] |
| - | [[Category: Sandy, J]] | + | [[Category: Rodrigues-Lima F]] |
| - | [[Category: Sim, E]] | + | [[Category: Sandy J]] |
| - | [[Category: Acyltransferase]]
| + | [[Category: Sim E]] |
| - | [[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
The NATs (arylamine N-acetyltransferases) are a well documented family of enzymes found in both prokaryotes and eukaryotes. NATs are responsible for the acetylation of a range of arylamine, arylhydrazine and hydrazine compounds. We present here an investigation into the catalytic triad of residues (Cys-His-Asp) and other structural features of NATs using a variety of methods, including site-directed mutagenesis, X-ray crystallography and bioinformatics analysis, in order to investigate whether each of the residues of the catalytic triad is essential for catalytic activity. The catalytic triad of residues, Cys-His-Asp, is a well defined motif present in several families of enzymes. We mutated each of the catalytic residues in turn to investigate the role they play in catalysis. We also mutated a key residue, Gly126, implicated in acetyl-CoA binding, to examine the effects on acetylation activity. In addition, we have solved the structure of a C70Q mutant of Mycobacterium smegmatis NAT to a resolution of 1.45 A (where 1 A=0.1 nm). This structure confirms that the mutated protein is correctly folded, and provides a structural model for an acetylated NAT intermediate. Our bioinformatics investigation analysed the extent of sequence conservation between all eukaryotic and prokaryotic NAT enzymes for which sequence data are available. This revealed several new sequences, not yet reported, of NAT paralogues. Together, these studies have provided insight into the fundamental core of NAT enzymes, and the regions where sequence differences account for the functional diversity of this family. We have confirmed that each of the three residues of the triad is essential for acetylation activity.
Investigation of the catalytic triad of arylamine N-acetyltransferases: essential residues required for acetyl transfer to arylamines.,Sandy J, Mushtaq A, Holton SJ, Schartau P, Noble ME, Sim E Biochem J. 2005 Aug 15;390(Pt 1):115-23. PMID:15869465[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, Holton SJ, Schartau P, Noble ME, Sim E. Investigation of the catalytic triad of arylamine N-acetyltransferases: essential residues required for acetyl transfer to arylamines. Biochem J. 2005 Aug 15;390(Pt 1):115-23. PMID:15869465 doi:10.1042/BJ20050277
|
