View source for 6iiy


==Crystal structure of deacetylase triple mutant (Orf2*T) that involving in teicoplanin biosynthetic pathway==
<StructureSection load='6iiy' size='340' side='right'caption='[[6iiy]], [[Resolution|resolution]] 1.29&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6iiy]] 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=6IIY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6IIY 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]] 1.29&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</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=6iiy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6iiy OCA], [https://pdbe.org/6iiy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6iiy RCSB], [https://www.ebi.ac.uk/pdbsum/6iiy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6iiy ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q6ZZJ1_ACTTI Q6ZZJ1_ACTTI] 
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== Publication Abstract from PubMed ==
Lipoglycopeptide antibiotics, for example, teicoplanin (Tei) and A40926, are more potent than vancomycin against Gram-positive (Gram-(+)) drug-resistant pathogens, for example, methicillin-resistant Staphylococcus aureus (MRSA). To extend their therapeutic effectiveness on vancomycin-resistant S. aureus (VRSA), the biosynthetic pathway of the N-acyl glucosamine (Glc) pharmacophore at residue 4 (r4) of teicoplanin pseudoaglycone redirection to residue 6 (r6) was attempted. On the basis of crystal structures, two regioselective biocatalysts Orf2*T (a triple-mutation mutant S98A/V121A/F193Y) and Orf11*S (a single-mutation mutant W163A) were engineered, allowing them to act on GlcNAc at r6. New analogs thereby made show marked antimicrobial activity against MRSA and VRSA by 2-3 orders of magnitude better than teicoplanin and vancomycin. The lipid side chain of the Tei-analogs armed with a terminal mono- or diguanidino group extends the antimicrobial specificity from Gram-(+) to Gram-negative (Gram-(-)), comparable to that of kanamycin. In addition to low cytotoxicity and high safety, the Tei analogs exhibit new modes of action as a result of resensitization of VRSA and Acinetobacter baumannii. The redirection of the biosynthetic pathway for the N-acyl-Glc pharmacophore from r4 to r6 bodes well for large-scale production of selected r6,Tei congeners in an environmentally friendly synthetic biology approach.

Teicoplanin Reprogrammed with the N-Acyl-Glucosamine Pharmacophore at the Penultimate Residue of Aglycone Acquires Broad-Spectrum Antimicrobial Activities Effectively Killing Gram-Positive and -Negative Pathogens.,Huang CM, Lyu SY, Lin KH, Chen CL, Chen MH, Shih HW, Hsu NS, Lo IW, Wang YL, Li YS, Wu CJ, Li TL ACS Infect Dis. 2019 Mar 8;5(3):430-442. doi: 10.1021/acsinfecdis.8b00317. Epub, 2019 Jan 11. PMID:30599088<ref>PMID:30599088</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6iiy" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Actinoplanes teichomyceticus]]
[[Category: Large Structures]]
[[Category: Huang CM]]
[[Category: Li TL]]