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| | ==The crystal structure of acyltransferase in complex with decanoyl-CoA and Tei pseudoaglycone== | | ==The crystal structure of acyltransferase in complex with decanoyl-CoA and Tei pseudoaglycone== |
| - | <StructureSection load='4mfp' size='340' side='right' caption='[[4mfp]], [[Resolution|resolution]] 2.15Å' scene=''> | + | <StructureSection load='4mfp' size='340' side='right'caption='[[4mfp]], [[Resolution|resolution]] 2.15Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4mfp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Actinoplanes_teichomyceticus Actinoplanes teichomyceticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MFP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MFP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4mfp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Actinoplanes_teichomyceticus Actinoplanes teichomyceticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MFP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MFP FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=DKA:DECANOIC+ACID'>DKA</scene>, <scene name='pdbligand=GCS:D-GLUCOSAMINE'>GCS</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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]] 2.15Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=3FG:(2S)-AMINO(3,5-DIHYDROXYPHENYL)ETHANOIC+ACID'>3FG</scene>, <scene name='pdbligand=3MY:3-CHLORO-D-TYROSINE'>3MY</scene>, <scene name='pdbligand=GHP:(2R)-AMINO(4-HYDROXYPHENYL)ETHANOIC+ACID'>GHP</scene>, <scene name='pdbligand=OMY:(BETAR)-3-CHLORO-BETA-HYDROXY-L-TYROSINE'>OMY</scene></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3FG:(2S)-AMINO(3,5-DIHYDROXYPHENYL)ETHANOIC+ACID'>3FG</scene>, <scene name='pdbligand=3MY:3-CHLORO-D-TYROSINE'>3MY</scene>, <scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=DKA:DECANOIC+ACID'>DKA</scene>, <scene name='pdbligand=GCS:D-GLUCOSAMINE'>GCS</scene>, <scene name='pdbligand=GHP:(2R)-AMINO(4-HYDROXYPHENYL)ETHANOIC+ACID'>GHP</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=OMY:(BETAR)-3-CHLORO-BETA-HYDROXY-L-TYROSINE'>OMY</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4mfj|4mfj]], [[4mfk|4mfk]], [[4mfl|4mfl]], [[4mfq|4mfq]], [[4mfs|4mfs]], [[4mft|4mft]], [[4mfw|4mfw]], [[4mfx|4mfx]], [[4mfy|4mfy]], [[4mg0|4mg0]], [[4mg1|4mg1]]</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=4mfp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mfp OCA], [https://pdbe.org/4mfp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mfp RCSB], [https://www.ebi.ac.uk/pdbsum/4mfp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mfp ProSAT]</span></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=4mfp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mfp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4mfp RCSB], [http://www.ebi.ac.uk/pdbsum/4mfp PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q70AY4_ACTTI Q70AY4_ACTTI] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4mfp" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Actinoplanes teichomyceticus]] | | [[Category: Actinoplanes teichomyceticus]] |
| - | [[Category: Chang, C Y]] | + | [[Category: Large Structures]] |
| - | [[Category: Huang, C J]] | + | [[Category: Chang CY]] |
| - | [[Category: Li, T L]] | + | [[Category: Huang CJ]] |
| - | [[Category: Liu, Y C]] | + | [[Category: Li TL]] |
| - | [[Category: Lyu, S Y]] | + | [[Category: Liu YC]] |
| - | [[Category: Acyl-coa]] | + | [[Category: Lyu SY]] |
| - | [[Category: Acyltransferase]]
| + | |
| - | [[Category: Gnat]]
| + | |
| - | [[Category: Transferase-antibiotic complex]]
| + | |
| Structural highlights
4mfp is a 2 chain structure with sequence from Actinoplanes teichomyceticus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.15Å |
| Ligands: | , , , , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
Q70AY4_ACTTI
Publication Abstract from PubMed
Teicoplanin A2-2 (Tei)/A40926 is the last-line antibiotic to treat multidrug-resistant Gram-positive bacterial infections, e.g., methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE). This class of antibiotics is powered by the N-acyltransferase (NAT) Orf11*/Dbv8 through N-acylation on glucosamine at the central residue of Tei/A40926 pseudoaglycone. The NAT enzyme possesses enormous value in untapped applications; its advanced development is hampered largely due to a lack of structural information. In this report, we present eight high-resolution X-ray crystallographic unary, binary, and ternary complexes in order to decipher the molecular basis for NAT's functionality. The enzyme undergoes a multistage conformational change upon binding of acyl-CoA, thus allowing the uploading of Tei pseudoaglycone to enable the acyl-transfer reaction to take place in the occlusion between the N- and C-halves of the protein. The acyl moiety of acyl-CoA can be bulky or lengthy, allowing a large extent of diversity in new derivatives that can be formed upon its transfer. Vancomycin/synthetic acyl-N-acetyl cysteamine was not expected to be able to serve as a surrogate for an acyl acceptor/donor, respectively. Most strikingly, NAT can catalyze formation of 2-N,6-O-diacylated or C6-->C2 acyl-substituted Tei analogues through an unusual 1,4-migration mechanism under stoichiometric/solvational reaction control, wherein selected representatives showed excellent biological activities, effectively counteracting major types (VanABC) of VRE.
Multiple complexes of long aliphatic N-acyltransferases lead to synthesis of 2,6-diacylated/2-acyl-substituted glycopeptide antibiotics, effectively killing vancomycin-resistant enterococcus.,Lyu SY, Liu YC, Chang CY, Huang CJ, Chiu YH, Huang CM, Hsu NS, Lin KH, Wu CJ, Tsai MD, Li TL J Am Chem Soc. 2014 Aug 6;136(31):10989-95. doi: 10.1021/ja504125v. Epub 2014 Jul, 25. PMID:25095906[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lyu SY, Liu YC, Chang CY, Huang CJ, Chiu YH, Huang CM, Hsu NS, Lin KH, Wu CJ, Tsai MD, Li TL. Multiple complexes of long aliphatic N-acyltransferases lead to synthesis of 2,6-diacylated/2-acyl-substituted glycopeptide antibiotics, effectively killing vancomycin-resistant enterococcus. J Am Chem Soc. 2014 Aug 6;136(31):10989-95. doi: 10.1021/ja504125v. Epub 2014 Jul, 25. PMID:25095906 doi:http://dx.doi.org/10.1021/ja504125v
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