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[[Image:2nsl.gif|left|200px]]
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{{STRUCTURE_2nsl|  PDB=2nsl  |  SCENE=  }}
'''E. coli PurE H45N mutant complexed with CAIR'''


==E. coli PurE H45N mutant complexed with CAIR==
<StructureSection load='2nsl' size='340' side='right'caption='[[2nsl]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2nsl]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NSL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NSL 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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C2R:5-AMINO-1-(5-O-PHOSPHONO-BETA-D-RIBOFURANOSYL)-1H-IMIDAZOLE-4-CARBOXYLIC+ACID'>C2R</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=2nsl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nsl OCA], [https://pdbe.org/2nsl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2nsl RCSB], [https://www.ebi.ac.uk/pdbsum/2nsl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2nsl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PURE_ECOLI PURE_ECOLI] Catalyzes the conversion of N5-carboxyaminoimidazole ribonucleotide (N5-CAIR) to 4-carboxy-5-aminoimidazole ribonucleotide (CAIR).
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ns/2nsl_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2nsl ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
N5-Carboxyaminoimidazole ribonucleotide mutase (N5-CAIR mutase or PurE) from Escherichia coli catalyzes the reversible interconversion of N5-CAIR to carboxyaminoimidazole ribonucleotide (CAIR) with direct CO2 transfer. Site-directed mutagenesis, a pH-rate profile, DFT calculations, and X-ray crystallography together provide new insight into the mechanism of this unusual transformation. These studies suggest that a conserved, protonated histidine (His45) plays an essential role in catalysis. The importance of proton transfers is supported by DFT calculations on CAIR and N5-CAIR analogues in which the ribose 5'-phosphate is replaced with a methyl group. The calculations suggest that the nonaromatic tautomer of CAIR (isoCAIR) is only 3.1 kcal/mol higher in energy than its aromatic counterpart, implicating this species as a potential intermediate in the PurE-catalyzed reaction. A structure of wild-type PurE cocrystallized with 4-nitroaminoimidazole ribonucleotide (NO2-AIR, a CAIR analogue) and structures of H45N and H45Q PurEs soaked with CAIR have been determined and provide the first insight into the binding of an intact PurE substrate. A comparison of 19 available structures of PurE and PurE mutants in apo and nucleotide-bound forms reveals a common, buried carboxylate or CO2 binding site for CAIR and N5-CAIR in a hydrophobic pocket in which the carboxylate or CO2 interacts with backbone amides. This work has led to a mechanistic proposal in which the carboxylate orients the substrate for proton transfer from His45 to N5-CAIR to form an enzyme-bound aminoimidazole ribonucleotide (AIR) and CO2 intermediate. Subsequent movement of the aminoimidazole moiety of AIR reorients it for addition of CO2 at C4 to generate isoCAIR. His45 is now in a position to remove a C4 proton to produce CAIR.


==Overview==
N5-CAIR mutase: role of a CO2 binding site and substrate movement in catalysis.,Hoskins AA, Morar M, Kappock TJ, Mathews II, Zaugg JB, Barder TE, Peng P, Okamoto A, Ealick SE, Stubbe J Biochemistry. 2007 Mar 13;46(10):2842-55. Epub 2007 Feb 14. PMID:17298082<ref>PMID:17298082</ref>
N5-Carboxyaminoimidazole ribonucleotide mutase (N5-CAIR mutase or PurE) from Escherichia coli catalyzes the reversible interconversion of N5-CAIR to carboxyaminoimidazole ribonucleotide (CAIR) with direct CO2 transfer. Site-directed mutagenesis, a pH-rate profile, DFT calculations, and X-ray crystallography together provide new insight into the mechanism of this unusual transformation. These studies suggest that a conserved, protonated histidine (His45) plays an essential role in catalysis. The importance of proton transfers is supported by DFT calculations on CAIR and N5-CAIR analogues in which the ribose 5'-phosphate is replaced with a methyl group. The calculations suggest that the nonaromatic tautomer of CAIR (isoCAIR) is only 3.1 kcal/mol higher in energy than its aromatic counterpart, implicating this species as a potential intermediate in the PurE-catalyzed reaction. A structure of wild-type PurE cocrystallized with 4-nitroaminoimidazole ribonucleotide (NO2-AIR, a CAIR analogue) and structures of H45N and H45Q PurEs soaked with CAIR have been determined and provide the first insight into the binding of an intact PurE substrate. A comparison of 19 available structures of PurE and PurE mutants in apo and nucleotide-bound forms reveals a common, buried carboxylate or CO2 binding site for CAIR and N5-CAIR in a hydrophobic pocket in which the carboxylate or CO2 interacts with backbone amides. This work has led to a mechanistic proposal in which the carboxylate orients the substrate for proton transfer from His45 to N5-CAIR to form an enzyme-bound aminoimidazole ribonucleotide (AIR) and CO2 intermediate. Subsequent movement of the aminoimidazole moiety of AIR reorients it for addition of CO2 at C4 to generate isoCAIR. His45 is now in a position to remove a C4 proton to produce CAIR.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
2NSL is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NSL OCA].
</div>
<div class="pdbe-citations 2nsl" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
N5-CAIR mutase: role of a CO2 binding site and substrate movement in catalysis., Hoskins AA, Morar M, Kappock TJ, Mathews II, Zaugg JB, Barder TE, Peng P, Okamoto A, Ealick SE, Stubbe J, Biochemistry. 2007 Mar 13;46(10):2842-55. Epub 2007 Feb 14. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17298082 17298082]
*[[Phosphoribosylaminoimidazole carboxylase 3D structures|Phosphoribosylaminoimidazole carboxylase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
[[Category: Phosphoribosylaminoimidazole carboxylase]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Ealick SE]]
[[Category: Ealick, S E.]]
[[Category: Morar M]]
[[Category: Morar, M.]]
[[Category: Central three layer alpha-beta-alpha sandwich]]
[[Category: Kinked c-terminal helix]]
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Retrieved from "https://proteopedia.org/2nsl"