View source for 7dq6


==Crystal structure of HitB in complex with (S)-beta-3-Br-phenylalanine sulfamoyladenosine==
<StructureSection load='7dq6' size='340' side='right'caption='[[7dq6]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7dq6]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Embleya_scabrispora Embleya scabrispora]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7DQ6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DQ6 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]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=HFR:[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methyl+N-[(3S)-3-azanyl-3-(3-bromophenyl)propanoyl]sulfamate'>HFR</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=7dq6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dq6 OCA], [https://pdbe.org/7dq6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dq6 RCSB], [https://www.ebi.ac.uk/pdbsum/7dq6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dq6 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A0F7R6G7_9ACTN A0A0F7R6G7_9ACTN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Hitachimycin is a macrolactam antibiotic with an (S)-beta-phenylalanine (beta-Phe) at the starter position of its polyketide skeleton. (S)-beta-Phe is formed from l-alpha-phenylalanine by the phenylananine-2,3-aminomutase HitA in the hitachimycin biosynthetic pathway. In this study, we produced new hitachimycin analogs via mutasynthesis by feeding various (S)-beta-Phe analogs to a DeltahitA strain. We obtained six hitachimycin analogs with F at the ortho, meta, or para position and Cl, Br, or a CH3 group at the meta position of the phenyl moiety, as well as two hitachimycin analogs with thienyl substitutions. Furthermore, we carried out a biochemical and structural analysis of HitB, a beta-amino acid-selective adenylation enzyme that introduces (S)-beta-Phe into the hitachimycin biosynthetic pathway. The KM values of the incorporated (S)-beta-Phe analogs and natural (S)-beta-Phe were similar. However, the KM values of unincorporated (S)-beta-Phe analogs with Br and a CH3 group at the ortho or para position of the phenyl moiety were high, indicating that HitB functions as a gatekeeper to select macrolactam starter units during mutasynthesis. The crystal structure of HitB in complex with (S)-beta-3-Br-phenylalanine sulfamoyladenosine (beta-m-Br-Phe-SA) revealed that the bulky meta-Br group is accommodated by the conformational flexibility around Phe328, whose side chain is close to the meta position. The aromatic group of beta-m-Br-Phe-SA is surrounded by hydrophobic and aromatic residues, which appears to confer the conformational flexibility that enables HitB to accommodate the meta-substituted (S)-beta-Phe. The new hitachimycin analogs exhibited different levels of biological activity in HeLa cells and multidrug-sensitive budding yeast, suggesting that they may target different molecules.

Mutational Biosynthesis of Hitachimycin Analogs Controlled by the beta-Amino Acid-Selective Adenylation Enzyme HitB.,Kudo F, Takahashi S, Miyanaga A, Nakazawa Y, Nishino K, Hayakawa Y, Kawamura K, Ishikawa F, Tanabe G, Iwai N, Nagumo Y, Usui T, Eguchi T ACS Chem Biol. 2021 Feb 24. doi: 10.1021/acschembio.1c00003. PMID:33625847<ref>PMID:33625847</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7dq6" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Embleya scabrispora]]
[[Category: Large Structures]]
[[Category: Eguchi T]]
[[Category: Kudo F]]
[[Category: Miyanaga A]]
[[Category: Nakazawa Y]]
[[Category: Takahashi S]]