View source for 7csi


==Aminoglycoside 2'-N-acetyltransferase from Mycolicibacterium smegmatis-Complex with Coenzyme A and Sisomicin==
<StructureSection load='7csi' size='340' side='right'caption='[[7csi]], [[Resolution|resolution]] 1.89&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7csi]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycolicibacterium_smegmatis_MC2_155 Mycolicibacterium smegmatis MC2 155]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CSI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CSI 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]] 1.89&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=SIS:(1S,2S,3R,4S,6R)-4,6-DIAMINO-3-{[(2S,3R)-3-AMINO-6-(AMINOMETHYL)-3,4-DIHYDRO-2H-PYRAN-2-YL]OXY}-2-HYDROXYCYCLOHEXYL+3-DEOXY-4-C-METHYL-3-(METHYLAMINO)-BETA-L-ARABINOPYRANOSIDE'>SIS</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=7csi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7csi OCA], [https://pdbe.org/7csi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7csi RCSB], [https://www.ebi.ac.uk/pdbsum/7csi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7csi ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/AAC2_MYCS2 AAC2_MYCS2] Catalyzes the coenzyme A-dependent acetylation of the 2' hydroxyl or amino group of a broad spectrum of aminoglycosides. It confers resistance to aminoglycosides.<ref>PMID:9159528</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The expression of aminoglycoside-modifying enzymes represents a survival strategy of antibiotic-resistant bacteria. Aminoglycoside 2'-N-acetyltransferase [AAC(2')] neutralizes aminoglycoside drugs by acetylation of their 2' amino groups in an acetyl coenzyme A (CoA)-dependent manner. To understand the structural features and molecular mechanism underlying AAC(2') activity, we overexpressed, purified, and crystallized AAC(2') from Mycolicibacterium smegmatis [AAC(2')-Id] and determined the crystal structures of its apo-form and ternary complexes with CoA and four different aminoglycosides (gentamicin, sisomicin, neomycin, and paromomycin). These AAC(2')-Id structures unraveled the binding modes of different aminoglycosides, explaining the broad substrate specificity of the enzyme. Comparative structural analysis showed that the alpha4-helix and beta8-beta9 loop region undergo major conformational changes upon CoA and substrate binding. Additionally, structural comparison between the present paromomycin-bound AAC(2')-Id structure and the previously reported paromomycin-bound AAC(6')-Ib and 30S ribosome structures revealed the structural features of paromomycin that are responsible for its antibiotic activity and AAC binding. Taken together, these results provide useful information for designing AAC(2') inhibitors and for the chemical modification of aminoglycosides.

Structural and biochemical analyses of an aminoglycoside 2'-N-acetyltransferase from Mycolicibacterium smegmatis.,Jeong CS, Hwang J, Do H, Cha SS, Oh TJ, Kim HJ, Park HH, Lee JH Sci Rep. 2020 Dec 9;10(1):21503. doi: 10.1038/s41598-020-78699-z. PMID:33299080<ref>PMID:33299080</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7csi" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycolicibacterium smegmatis MC2 155]]
[[Category: Do H]]
[[Category: Hwang J]]
[[Category: Jeong CS]]
[[Category: Lee JH]]