1y1i

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(New page: 200px<br /> <applet load="1y1i" size="450" color="white" frame="true" align="right" spinBox="true" caption="1y1i, resolution 2.61&Aring;" /> '''hyuman formylglycin...)
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[[Image:1y1i.gif|left|200px]]<br />
 
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<applet load="1y1i" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1y1i, resolution 2.61&Aring;" />
 
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'''hyuman formylglycine generating enzyme, reduced form'''<br />
 
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==Overview==
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==hyuman formylglycine generating enzyme, reduced form==
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Sulfatases are enzymes essential for degradation and remodeling of sulfate, esters. Formylglycine (FGly), the key catalytic residue in the active, site, is unique to sulfatases. In higher eukaryotes, FGly is generated, from a cysteine precursor by the FGly-generating enzyme (FGE). Inactivity, of FGE results in multiple sulfatase deficiency (MSD), a fatal autosomal, recessive syndrome. Based on the crystal structure, we report that FGE is, a single-domain monomer with a surprising paucity of secondary structure, and adopts a unique fold. The effect of all 18 missense mutations found in, MSD patients is explained by the FGE structure, providing a molecular, basis of MSD. The catalytic mechanism of FGly generation was elucidated by, six high-resolution structures of FGE in different redox environments. The, structures allow formulation of a novel oxygenase mechanism whereby FGE, utilizes molecular oxygen to generate FGly via a cysteine sulfenic acid, intermediate.
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<StructureSection load='1y1i' size='340' side='right'caption='[[1y1i]], [[Resolution|resolution]] 2.61&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1y1i]] is a 1 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=1Y1I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Y1I FirstGlance]. <br>
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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]] 2.61&#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=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=1y1i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y1i OCA], [https://pdbe.org/1y1i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1y1i RCSB], [https://www.ebi.ac.uk/pdbsum/1y1i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1y1i ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/SUMF1_HUMAN SUMF1_HUMAN] Defects in SUMF1 are the cause of multiple sulfatase deficiency (MSD) [MIM:[https://omim.org/entry/272200 272200]. MSD is a clinically and biochemically heterogeneous disorder caused by the simultaneous impairment of all sulfatases, due to defective post-translational modification and activation. It combines features of individual sulfatase deficiencies such as metachromatic leukodystrophy, mucopolysaccharidosis, chondrodysplasia punctata, hydrocephalus, ichthyosis, neurologic deterioration and developmental delay. Inheritance is autosomal recessive.<ref>PMID:12757706</ref> <ref>PMID:12757705</ref> <ref>PMID:15146462</ref> <ref>PMID:18157819</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/SUMF1_HUMAN SUMF1_HUMAN] Using molecular oxygen and an unidentified reducing agent, oxidizes a cysteine residue in the substrate sulfatase to an active site 3-oxoalanine residue, which is also called C(alpha)-formylglycine. Known substrates include GALNS, ARSA, STS and ARSE.<ref>PMID:12757706</ref> <ref>PMID:15657036</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/y1/1y1i_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1y1i 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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Sulfatases are enzymes essential for degradation and remodeling of sulfate esters. Formylglycine (FGly), the key catalytic residue in the active site, is unique to sulfatases. In higher eukaryotes, FGly is generated from a cysteine precursor by the FGly-generating enzyme (FGE). Inactivity of FGE results in multiple sulfatase deficiency (MSD), a fatal autosomal recessive syndrome. Based on the crystal structure, we report that FGE is a single-domain monomer with a surprising paucity of secondary structure and adopts a unique fold. The effect of all 18 missense mutations found in MSD patients is explained by the FGE structure, providing a molecular basis of MSD. The catalytic mechanism of FGly generation was elucidated by six high-resolution structures of FGE in different redox environments. The structures allow formulation of a novel oxygenase mechanism whereby FGE utilizes molecular oxygen to generate FGly via a cysteine sulfenic acid intermediate.
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==Disease==
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Molecular basis for multiple sulfatase deficiency and mechanism for formylglycine generation of the human formylglycine-generating enzyme.,Dierks T, Dickmanns A, Preusser-Kunze A, Schmidt B, Mariappan M, von Figura K, Ficner R, Rudolph MG Cell. 2005 May 20;121(4):541-52. PMID:15907468<ref>PMID:15907468</ref>
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Known disease associated with this structure: Multiple sulfatase deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607939 607939]]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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1Y1I is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1Y1I OCA].
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</div>
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<div class="pdbe-citations 1y1i" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Molecular basis for multiple sulfatase deficiency and mechanism for formylglycine generation of the human formylglycine-generating enzyme., Dierks T, Dickmanns A, Preusser-Kunze A, Schmidt B, Mariappan M, von Figura K, Ficner R, Rudolph MG, Cell. 2005 May 20;121(4):541-52. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15907468 15907468]
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*[[Sulfatase-modifying factor|Sulfatase-modifying factor]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[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: Dickmanns, A.]]
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[[Category: Dickmanns A]]
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[[Category: Ficner, R.]]
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[[Category: Ficner R]]
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[[Category: Rudolph, M.G.]]
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[[Category: Rudolph MG]]
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[[Category: CA]]
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[[Category: cysteine sulfenic acid]]
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[[Category: formylglycine]]
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[[Category: multiple sulfatase deficiency]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:13:36 2007''
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Current revision

hyuman formylglycine generating enzyme, reduced form

PDB ID 1y1i

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