View source for 8sbm


==Crystal structure of the wild-type Catalytic ATP-binding domain of Mtb DosS==
<StructureSection load='8sbm' size='340' side='right'caption='[[8sbm]], [[Resolution|resolution]] 1.47&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8sbm]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8SBM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SBM 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]] 1.47&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=8sbm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8sbm OCA], [https://pdbe.org/8sbm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8sbm RCSB], [https://www.ebi.ac.uk/pdbsum/8sbm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8sbm ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A9Q6PM98_MYCTX A0A9Q6PM98_MYCTX] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
DosS is a heme-containing histidine kinase that triggers dormancy transformation inMycobacterium tuberculosis. Sequence comparison of the catalytic ATP-binding (CA) domain of DosS to other well-studied histidine kinases reveals a short ATP-lid. This feature has been thought to block binding of ATP to DosS's CA domain in the absence of interactions with DosS's dimerization and histidine phospho-transfer (DHp) domain. Here, we use a combination of computational modeling, structural biology, and biophysical studies to re-examine ATP-binding modalities in DosS. We show that the closed-lid conformation observed in crystal structures of DosS CA is caused by the presence of Zn(2+) in the ATP binding pocket that coordinates with Glu537 on the ATP-lid. Furthermore, circular dichroism studies and comparisons of DosS CA's crystal structure with its AlphaFold model and homologous DesK reveal that residues 503-507 that appear as a random coil in the Zn(2+)-coordinated crystal structure are in fact part of the N-box alpha helix needed for efficient ATP binding. Such random-coil transformation of an N-box alpha helix turn and the closed-lid conformation are both artifacts arising from large millimolar Zn(2+) concentrations used in DosS CA crystallization buffers. In contrast, in the absence of Zn(2+), the short ATP-lid of DosS CA has significant conformational flexibility and can effectively bind AMP-PNP (K(d) = 53 +/- 13 muM), a non-hydrolyzable ATP analog. Furthermore, the nucleotide affinity remains unchanged when CA is conjugated to the DHp domain (K(d) = 51 +/- 6 muM). In all, our findings reveal that the short ATP-lid of DosS CA does not hinder ATP binding and provide insights that extend to 2988 homologous bacterial proteins containing such ATP-lids.

Understanding ATP Binding to DosS Catalytic Domain with a Short ATP-Lid.,Larson GW, Windsor PK, Smithwick E, Shi K, Aihara H, Rama Damodaran A, Bhagi-Damodaran A Biochemistry. 2023 Oct 31. doi: 10.1021/acs.biochem.3c00306. PMID:37905955<ref>PMID:37905955</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8sbm" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Aihara H]]
[[Category: Bhagi-Damodaran A]]
[[Category: Larson G]]
[[Category: Shi K]]