This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

4q36

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 08:19, 11 August 2016

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

Structural highlights

4q36 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, 4q38
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/4q36"

@@ Line 1: / Line 1: @@
 ==The crystal structure of acyltransferase in complex with octanoyl-CoA and teicoplanin==
 <StructureSection load='4q36' size='340' side='right' caption='[[4q36]], [[Resolution|resolution]] 2.35&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=CO8:OCTANOYL-COENZYME+A'>CO8</scene>, <scene name='pdbligand=GCS:D-GLUCOSAMINE'>GCS</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]], [[4q38|4q38]]</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=4q36 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q36 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4q36 RCSB], [http://www.ebi.ac.uk/pdbsum/4q36 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=4q36 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q36 OCA], [http://pdbe.org/4q36 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4q36 RCSB], [http://www.ebi.ac.uk/pdbsum/4q36 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4q36 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 4q36" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4q36

From Proteopedia

Revision as of 08:19, 11 August 2016

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

Structural highlights

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox