1pl0

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{{Seed}}
 
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[[Image:1pl0.png|left|200px]]
 
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==Crystal structure of human ATIC in complex with folate-based inhibitor, BW2315U89UC==
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The line below this paragraph, containing "STRUCTURE_1pl0", creates the "Structure Box" on the page.
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<StructureSection load='1pl0' size='340' side='right'caption='[[1pl0]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1pl0]] is a 4 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=1PL0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PL0 FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 2.6&#8491;</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=AMZ:AMINOIMIDAZOLE+4-CARBOXAMIDE+RIBONUCLEOTIDE'>AMZ</scene>, <scene name='pdbligand=BW2:N-(4-{[(2-AMINO-4-OXO-3,4-DIHYDROQUINAZOLIN-6-YL)AMINO]SULFONYL}BENZOYL)GLUTAMIC+ACID'>BW2</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=XMP:XANTHOSINE-5-MONOPHOSPHATE'>XMP</scene></td></tr>
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{{STRUCTURE_1pl0| PDB=1pl0 | SCENE= }}
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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=1pl0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pl0 OCA], [https://pdbe.org/1pl0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pl0 RCSB], [https://www.ebi.ac.uk/pdbsum/1pl0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pl0 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/PUR9_HUMAN PUR9_HUMAN] Defects in ATIC are the cause of AICAR transformylase/IMP cyclohydrolase deficiency (AICAR) [MIM:[https://omim.org/entry/608688 608688]. A neurologically devastating inborn error of purine biosynthesis. Patients excrete massive amounts of AICA-riboside in the urine and accumulate AICA-ribotide and its derivatives in erythrocytes and fibroblasts. AICAR causes profound mental retardation, epilepsy, dysmorphic features and congenital blindness.<ref>PMID:14966129</ref> <ref>PMID:15114530</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/PUR9_HUMAN PUR9_HUMAN] Bifunctional enzyme that catalyzes 2 steps in purine biosynthesis.<ref>PMID:14966129</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pl/1pl0_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1pl0 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase/IMP cyclohydrolase (ATIC) is a bifunctional enzyme with folate-dependent AICAR transformylase and IMP cyclohydrolase activities that catalyzes the last two steps of purine biosynthesis. The AICAR transformylase inhibitors BW1540 and BW2315 are sulfamido-bridged 5,8-dideazafolate analogs with remarkably potent K(i) values of 8 and 6 nm, respectively, compared with most other antifolates. Crystal structures of ATIC at 2.55 and 2.60 A with each inhibitor, in the presence of substrate AICAR, revealed that the sulfonyl groups dominate inhibitor binding and orientation through interaction with the proposed oxyanion hole. These agents then appear to mimic the anionic transition state and now implicate Asn(431') in the reaction mechanism along with previously identified key catalytic residues Lys(266) and His(267). Potent and selective inhibition of the AICAR transformylase active site, compared with other folate-dependent enzymes, should therefore be pursued by further design of sulfonyl-containing antifolates.
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===Crystal structure of human ATIC in complex with folate-based inhibitor, BW2315U89UC===
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Crystal structures of human bifunctional enzyme aminoimidazole-4-carboxamide ribonucleotide transformylase/IMP cyclohydrolase in complex with potent sulfonyl-containing antifolates.,Cheong CG, Wolan DW, Greasley SE, Horton PA, Beardsley GP, Wilson IA J Biol Chem. 2004 Apr 23;279(17):18034-45. Epub 2004 Feb 13. PMID:14966129<ref>PMID:14966129</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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<div class="pdbe-citations 1pl0" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_14966129}}, adds the Publication Abstract to the page
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*[[Bifunctional purine biosynthesis protein PURH|Bifunctional purine biosynthesis protein PURH]]
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(as it appears on PubMed at http://www.pubmed.gov), where 14966129 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_14966129}}
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__TOC__
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</StructureSection>
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==Disease==
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Known disease associated with this structure: AICA-ribosiduria due to ATIC deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601731 601731]]
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==About this Structure==
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1PL0 is a [[Single protein]] structure of 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=1PL0 OCA].
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==Reference==
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Crystal structures of human bifunctional enzyme aminoimidazole-4-carboxamide ribonucleotide transformylase/IMP cyclohydrolase in complex with potent sulfonyl-containing antifolates., Cheong CG, Wolan DW, Greasley SE, Horton PA, Beardsley GP, Wilson IA, J Biol Chem. 2004 Apr 23;279(17):18034-45. Epub 2004 Feb 13. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14966129 14966129]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Beardsley, G P.]]
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[[Category: Beardsley GP]]
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[[Category: Cheong, C G.]]
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[[Category: Cheong CG]]
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[[Category: Greasley, S E.]]
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[[Category: Greasley SE]]
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[[Category: Horton, P A.]]
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[[Category: Horton PA]]
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[[Category: Wilson, I A.]]
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[[Category: Wilson IA]]
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[[Category: Aicar]]
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[[Category: Aicar transformylase]]
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[[Category: Bw2315u89uc]]
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[[Category: Folate-based inhibitor]]
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[[Category: Human atic]]
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[[Category: Imp cyclohydrolase]]
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[[Category: Xanthosine monophosphate]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 11:43:32 2008''
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Current revision

Crystal structure of human ATIC in complex with folate-based inhibitor, BW2315U89UC

PDB ID 1pl0

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