4eqg: Difference between revisions
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==Crystal structure of histidine triad nucleotide-binding protein 1 (HINT1) from human complexed with Ala-AMS== | ==Crystal structure of histidine triad nucleotide-binding protein 1 (HINT1) from human complexed with Ala-AMS== | ||
<StructureSection load='4eqg' size='340' side='right' caption='[[4eqg]], [[Resolution|resolution]] 1.52Å' scene=''> | <StructureSection load='4eqg' size='340' side='right'caption='[[4eqg]], [[Resolution|resolution]] 1.52Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4eqg]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4eqg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EQG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EQG FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A5A:5-O-(N-(L-ALANYL)-SULFAMOYL)ADENOSINE'>A5A</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A5A:5-O-(N-(L-ALANYL)-SULFAMOYL)ADENOSINE'>A5A</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</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=4eqg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eqg OCA], [https://pdbe.org/4eqg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4eqg RCSB], [https://www.ebi.ac.uk/pdbsum/4eqg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4eqg ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/HINT1_HUMAN HINT1_HUMAN] Hydrolyzes adenosine 5'-monophosphoramidate substrates such as AMP-morpholidate, AMP-N-alanine methyl ester, AMP-alpha-acetyl lysine methyl ester and AMP-NH2 (By similarity). | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 20: | Line 18: | ||
</div> | </div> | ||
<div class="pdbe-citations 4eqg" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 4eqg" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Histidine triad nucleotide-binding protein 3D structures|Histidine triad nucleotide-binding protein 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Fang P]] | ||
[[Category: | [[Category: Guo M]] | ||
[[Category: | [[Category: Wang J]] | ||
Revision as of 07:09, 7 October 2022
Crystal structure of histidine triad nucleotide-binding protein 1 (HINT1) from human complexed with Ala-AMSCrystal structure of histidine triad nucleotide-binding protein 1 (HINT1) from human complexed with Ala-AMS
Structural highlights
FunctionHINT1_HUMAN Hydrolyzes adenosine 5'-monophosphoramidate substrates such as AMP-morpholidate, AMP-N-alanine methyl ester, AMP-alpha-acetyl lysine methyl ester and AMP-NH2 (By similarity). Publication Abstract from PubMedHuman Hint1 suppresses specific gene transcription by interacting with the transcription factor MITF in mast cells. Hint1 activity is connected to lysyl-tRNA synthetase (LysRS), a member of the universal aminoacyl tRNA synthetase family that catalyzes specific aminoacylation of their cognate tRNAs, through an aminoacyl adenylate (aa-AMP) intermediate. During immune activation, LysRS produces a side-product diadenosine tetraphosphate (Ap(4)A) from the condensation of Lys-AMP with ATP. The pleiotropic signaling molecule Ap(4)A then binds Hint1 to promote activation of MITF-target gene transcription. Earlier work showed that Hint1 can also bind and hydrolyze Lys-AMP, possibly to constrain Ap(4)A production. Because Ap(4)A can result from condensation of other aa-AMP's with ATP, the specificity of the Hint1 aa-AMP-hydrolysis activity is of interest. Here we show that Hint1 has broad specificity for adenylate hydrolysis, whose structural basis we revealed through high-resolution structures of Hint1 in complex with three different aa-AMP analogues. Hint1 recognizes only the common main chain of the aminoacyl moiety, and has no contact with the aa side chain. The alpha-amino group is anchored by a cation-pi interaction with Trp123 at the C-terminus of Hint1. These results reveal the structural basis for the remarkable adenylate surveillance activity of Hint1, to potentially control Ap(4)A levels in the cell. Side Chain Independent Recognition of Aminoacyl Adenylates by the Hint1 Transcription Suppressor.,Wang J, Fang P, Schimmel P, Guo M J Phys Chem B. 2012 Mar 2. PMID:22329685[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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