3o1c: Difference between revisions
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==High resolution crystal structure of histidine triad nucleotide-binding protein 1 (Hint1) C38A mutant from rabbit complexed with Adenosine== | ==High resolution crystal structure of histidine triad nucleotide-binding protein 1 (Hint1) C38A mutant from rabbit complexed with Adenosine== | ||
<StructureSection load='3o1c' size='340' side='right' caption='[[3o1c]], [[Resolution|resolution]] 1.08Å' scene=''> | <StructureSection load='3o1c' size='340' side='right'caption='[[3o1c]], [[Resolution|resolution]] 1.08Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3o1c]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3o1c]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O1C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3O1C FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.08Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADN:ADENOSINE'>ADN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=3o1c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o1c OCA], [https://pdbe.org/3o1c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3o1c RCSB], [https://www.ebi.ac.uk/pdbsum/3o1c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3o1c 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_RABIT HINT1_RABIT] Hydrolyzes adenosine 5'-monophosphoramidate substrates such as AMP-morpholidate, AMP-N-alanine methyl ester, AMP-alpha-acetyl lysine methyl ester and AMP-NH2. | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/o1/3o1c_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/o1/3o1c_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
| Line 32: | Line 31: | ||
==See Also== | ==See Also== | ||
*[[Histidine triad nucleotide-binding protein|Histidine triad nucleotide-binding protein]] | *[[Histidine triad nucleotide-binding protein 3D structures|Histidine triad nucleotide-binding protein 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Dolot | [[Category: Oryctolagus cuniculus]] | ||
[[Category: Krakowiak | [[Category: Dolot RM]] | ||
[[Category: Nawrot | [[Category: Krakowiak AK]] | ||
[[Category: Ozga | [[Category: Nawrot B]] | ||
[[Category: Stec | [[Category: Ozga M]] | ||
[[Category: Stec WJ]] | |||
Latest revision as of 12:25, 6 September 2023
High resolution crystal structure of histidine triad nucleotide-binding protein 1 (Hint1) C38A mutant from rabbit complexed with AdenosineHigh resolution crystal structure of histidine triad nucleotide-binding protein 1 (Hint1) C38A mutant from rabbit complexed with Adenosine
Structural highlights
FunctionHINT1_RABIT Hydrolyzes adenosine 5'-monophosphoramidate substrates such as AMP-morpholidate, AMP-N-alanine methyl ester, AMP-alpha-acetyl lysine methyl ester and AMP-NH2. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedNucleoside 5'-O-phosphorothioates are formed in vivo as primary products of hydrolysis of oligo(nucleoside phosphorothioate)s (PS-oligos) that are applied as antisense therapeutic molecules. The biodistribution of PS-oligos and their pharmacokinetics have been widely reported, but little is known about their subsequent decay inside the organism. We suggest that the enzyme responsible for nucleoside 5'-O-monophosphorothioate ((d)NMPS) metabolism could be histidine triad nucleotide-binding protein 1 (Hint-1), a phosphoramidase belonging to the histidine triad (HIT) superfamily that is present in all forms of life. An additional, but usually ignored, activity of Hint-1 is its ability to catalyze the conversion of adenosine 5'-O-monophosphorothioate (AMPS) to 5'-O-monophosphate (AMP). By mutagenetic and biochemical studies, we defined the active site of Hint-1 and the kinetic parameters of the desulfuration reaction (P-S bond cleavage). Additionally, crystallographic analysis (resolution from 1.08 to 1.37 A) of three engineered cysteine mutants showed the high similarity of their structures, which were not very different from the structure of WT Hint-1. Moreover, we found that not only AMPS but also other ribonucleoside and 2'-deoxyribonucleoside phosphorothioates are desulfurated by Hint-1 at the following relative rates: GMPS > AMPS > dGMPS >/= CMPS > UMPS > dAMPS >> dCMPS > TMPS, and during the reaction, hydrogen sulfide, which is thought to be the third gaseous mediator, was released. Histidine triad nucleotide-binding protein 1 (HINT-1) phosphoramidase transforms nucleoside 5'-O-phosphorothioates to nucleoside 5'-O-phosphates.,Ozga M, Dolot R, Janicka M, Kaczmarek R, Krakowiak A J Biol Chem. 2010 Dec 24;285(52):40809-18. Epub 2010 Oct 12. PMID:20940308[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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