View source for 4tx2


==Crystal structure of the X-domain from teicoplanin biosynthesis==
<StructureSection load='4tx2' size='340' side='right'caption='[[4tx2]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4tx2]] is a 1 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=4TX2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TX2 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]] 2.9&#8491;</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=4tx2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tx2 OCA], [https://pdbe.org/4tx2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4tx2 RCSB], [https://www.ebi.ac.uk/pdbsum/4tx2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4tx2 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q70AZ6_ACTTI Q70AZ6_ACTTI] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Non-ribosomal peptide synthetase (NRPS) mega-enzyme complexes are modular assembly lines that are involved in the biosynthesis of numerous peptide metabolites independently of the ribosome. The multiple interactions between catalytic domains within the NRPS machinery are further complemented by additional interactions with external enzymes, particularly focused on the final peptide maturation process. An important class of NRPS metabolites that require extensive external modification of the NRPS-bound peptide are the glycopeptide antibiotics (GPAs), which include vancomycin and teicoplanin. These clinically relevant peptide antibiotics undergo cytochrome P450-catalysed oxidative crosslinking of aromatic side chains to achieve their final, active conformation. However, the mechanism underlying the recruitment of the cytochrome P450 oxygenases to the NRPS-bound peptide was previously unknown. Here we show, through in vitro studies, that the X-domain, a conserved domain of unknown function present in the final module of all GPA NRPS machineries, is responsible for the recruitment of oxygenases to the NRPS-bound peptide to perform the essential side-chain crosslinking. X-ray crystallography shows that the X-domain is structurally related to condensation domains, but that its amino acid substitutions render it catalytically inactive. We found that the X-domain recruits cytochrome P450 oxygenases to the NRPS and determined the interface by solving the structure of a P450-X-domain complex. Additionally, we demonstrated that the modification of peptide precursors by oxygenases in vitro-in particular the installation of the second crosslink in GPA biosynthesis-occurs only in the presence of the X-domain. Our results indicate that the presentation of peptidyl carrier protein (PCP)-bound substrates for oxidation in GPA biosynthesis requires the presence of the NRPS X-domain to ensure conversion of the precursor peptide into a mature aglycone, and that the carrier protein domain alone is not always sufficient to generate a competent substrate for external cytochrome P450 oxygenases.

X-domain of peptide synthetases recruits oxygenases crucial for glycopeptide biosynthesis.,Haslinger K, Peschke M, Brieke C, Maximowitsch E, Cryle MJ Nature. 2015 Feb 9. doi: 10.1038/nature14141. PMID:25686610<ref>PMID:25686610</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4tx2" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Actinoplanes teichomyceticus]]
[[Category: Large Structures]]
[[Category: Cryle MJ]]
[[Category: Haslinger K]]
[[Category: Peschke M]]