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4eqg

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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==
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<StructureSection load='4eqg' size='340' side='right' caption='[[4eqg]], [[Resolution|resolution]] 1.52&Aring;' scene=''>
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<StructureSection load='4eqg' size='340' side='right'caption='[[4eqg]], [[Resolution|resolution]] 1.52&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4eqg]] is a 2 chain structure with sequence from [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EQG FirstGlance]. <br>
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<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>
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</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>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.52&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4eqe|4eqe]], [[4eqh|4eqh]]</td></tr>
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<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>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HINT1, HINT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<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>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4eqg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eqg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4eqg RCSB], [http://www.ebi.ac.uk/pdbsum/4eqg PDBsum]</span></td></tr>
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</table>
</table>
== Function ==
== Function ==
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[[http://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).
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[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).
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Human 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.
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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<ref>PMID:22329685</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==See Also==
==See Also==
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*[[Histidine triad nucleotide-binding protein|Histidine triad nucleotide-binding protein]]
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*[[Histidine triad nucleotide-binding protein 3D structures|Histidine triad nucleotide-binding protein 3D structures]]
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Fang, P]]
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[[Category: Large Structures]]
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[[Category: Guo, M]]
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[[Category: Fang P]]
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[[Category: Wang, J]]
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[[Category: Guo M]]
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[[Category: Hit domain]]
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[[Category: Wang J]]
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[[Category: Hydrolase]]
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Current revision

Crystal structure of histidine triad nucleotide-binding protein 1 (HINT1) from human complexed with Ala-AMS

PDB ID 4eqg

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