4mfl: Difference between revisions
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The | ==The crystal structure of acyltransferase in complex with decanoyl-CoA and Tei pseudoaglycone== | ||
<StructureSection load='4mfl' size='340' side='right'caption='[[4mfl]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4mfl]] 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=4MFL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MFL FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</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=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=MFK:DECANOYL-COA'>MFK</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4mfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mfl OCA], [https://pdbe.org/4mfl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mfl RCSB], [https://www.ebi.ac.uk/pdbsum/4mfl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mfl ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q70AY4_ACTTI Q70AY4_ACTTI] | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:25095906</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4mfl" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Actinoplanes teichomyceticus]] | |||
[[Category: Large Structures]] | |||
[[Category: Chang CY]] | |||
[[Category: Huang CJ]] | |||
[[Category: Li TL]] | |||
[[Category: Liu YC]] | |||
[[Category: Lyu SY]] | |||