1eep

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[[Image:1eep.jpg|left|200px]]
 
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==2.4 A RESOLUTION CRYSTAL STRUCTURE OF BORRELIA BURGDORFERI INOSINE 5'-MONPHOSPHATE DEHYDROGENASE IN COMPLEX WITH A SULFATE ION==
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The line below this paragraph, containing "STRUCTURE_1eep", creates the "Structure Box" on the page.
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<StructureSection load='1eep' size='340' side='right'caption='[[1eep]], [[Resolution|resolution]] 2.40&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'>[[1eep]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Borreliella_burgdorferi Borreliella burgdorferi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EEP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EEP 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]] 2.4&#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=SO4:SULFATE+ION'>SO4</scene></td></tr>
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{{STRUCTURE_1eep| PDB=1eep | 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=1eep FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1eep OCA], [https://pdbe.org/1eep PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1eep RCSB], [https://www.ebi.ac.uk/pdbsum/1eep PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1eep ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/IMDH_BORBU IMDH_BORBU] Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth. Essential for mouse infection by tick bite and critical for the survival in environments that appear to lack sufficient amounts of guanine, guanosine, and/or deoxyguanosine to support spirochete growth, such as mammalian host tissues.<ref>PMID:9268334</ref> <ref>PMID:19666713</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/ee/1eep_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=1eep ConSurf].
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<div style="clear:both"></div>
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'''2.4 A RESOLUTION CRYSTAL STRUCTURE OF BORRELIA BURGDORFERI INOSINE 5'-MONPHOSPHATE DEHYDROGENASE IN COMPLEX WITH A SULFATE ION'''
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==See Also==
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*[[Inosine monophosphate dehydrogenase 3D structures|Inosine monophosphate dehydrogenase 3D structures]]
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== References ==
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==Overview==
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<references/>
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The conversion of inosine 5'-monophosphate (IMP) to xanthosine 5'-monophosphate (XMP) is the committed and rate-limiting reaction in de novo guanine nucleotide biosynthesis. Inosine 5'- monophosphate dehydrogenase (IMPDH) is the enzyme that catalyzes the oxidation of IMP to XMP with the concomitant reduction of nicotinamide adenine dinucleotide (from NAD(+) to NADH). Because of its critical role in purine biosynthesis, IMPDH is a drug design target for anticancer, antiinfective, and immunosuppressive chemotherapy. We have determined the crystal structure of IMPDH from Borrelia burgdorferi, the bacterial spirochete that causes Lyme disease, with a sulfate ion bound in the IMP phosphate binding site. This is the first structure of IMPDH in the absence of substrate or cofactor where the active-site loop (loop 6), which contains the essential catalytic residue Cys 229, is clearly defined in the electron density. We report that a seven residue region of loop 6, including Cys229, is tilted more than 6 A away from its position in substrate- or substrate analogue-bound structures of IMPDH, suggestive of a conformational change. The location of this loop between beta6 and alpha6 links IMPDH to a family of beta/alpha barrel enzymes known to utilize this loop as a functional lid during catalysis. Least-squares minimization, root-mean-square deviation analysis, and inspection of the molecular surface of the loop 6 region in the substrate-free B. burgdorferi IMPDH and XMP-bound Chinese hamster IMPDH show that loop 6 follows a similar pattern of hinged rigid-body motion and indicates that IMPDH may be using loop 6 to bind and sequester substrate and to recruit an essential catalytic residue.
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__TOC__
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</StructureSection>
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==About this Structure==
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[[Category: Borreliella burgdorferi]]
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1EEP is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Borrelia_burgdorferi Borrelia burgdorferi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EEP OCA].
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[[Category: Large Structures]]
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[[Category: Cahoon M]]
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==Reference==
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[[Category: Hedstrom L]]
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Crystal structure at 2.4 A resolution of Borrelia burgdorferi inosine 5'-monophosphate dehydrogenase: evidence of a substrate-induced hinged-lid motion by loop 6., McMillan FM, Cahoon M, White A, Hedstrom L, Petsko GA, Ringe D, Biochemistry. 2000 Apr 18;39(15):4533-42. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10758003 10758003]
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[[Category: McMillan FM]]
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[[Category: Borrelia burgdorferi]]
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[[Category: Petsko GA]]
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[[Category: IMP dehydrogenase]]
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[[Category: Ringe D]]
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[[Category: Single protein]]
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[[Category: White A]]
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[[Category: Cahoon, M.]]
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[[Category: Hedstrom, L.]]
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[[Category: McMillan, F M.]]
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[[Category: Petsko, G A.]]
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[[Category: Ringe, D.]]
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[[Category: White, A.]]
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[[Category: Alpha-beta barrel]]
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[[Category: Imp dehydrogenase]]
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[[Category: Impdh]]
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[[Category: Loop-6]]
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[[Category: Purine biosynthesis]]
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[[Category: Tim barrel]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 15:00:16 2008''
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Current revision

2.4 A RESOLUTION CRYSTAL STRUCTURE OF BORRELIA BURGDORFERI INOSINE 5'-MONPHOSPHATE DEHYDROGENASE IN COMPLEX WITH A SULFATE ION

PDB ID 1eep

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