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4q38

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Revision as of 10:10, 11 August 2016

The crystal structure of acyltransferase in complex with decanoyl-CoA and teicoplanin

Structural highlights

4q38 is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	4mfj, 4q36
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

1 Structural highlights
2 Publication Abstract from PubMed
3 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4q38"

@@ Line 1: / Line 1: @@
 ==The crystal structure of acyltransferase in complex with decanoyl-CoA and teicoplanin==
 <StructureSection load='4q38' size='340' side='right' caption='[[4q38]], [[Resolution|resolution]] 1.99&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </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=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TEC:2-AMINO-6-O-DECANOYL-2-DEOXY-BETA-D-GLUCOPYRANOSE'>TEC</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4mfj|4mfj]], [[4q36|4q36]]</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=4q38 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q38 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4q38 RCSB], [http://www.ebi.ac.uk/pdbsum/4q38 PDBsum]</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=4q38 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q38 OCA], [http://pdbe.org/4q38 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4q38 RCSB], [http://www.ebi.ac.uk/pdbsum/4q38 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4q38 ProSAT]</span></td></tr>
 </table>
 <div style="background-color:#fffaf0;">
@@ Line 15: / Line 16: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4q38" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4q38

From Proteopedia

Revision as of 10:10, 11 August 2016

The crystal structure of acyltransferase in complex with decanoyl-CoA and teicoplanin

Structural highlights

Publication Abstract from PubMed

References

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Proteopedia Page Contributors and Editors (what is this?)

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