1n2l: Difference between revisions

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-{{Seed}}
-[[Image:1n2l.png|left|200px]]
-<!--
+==Crystal structure of a covalent intermediate of endogenous human arylsulfatase A==
-The line below this paragraph, containing "STRUCTURE_1n2l", creates the "Structure Box" on the page.
+<StructureSection load='1n2l' size='340' side='right'caption='[[1n2l]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[1n2l]] 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=1N2L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1N2L FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2&#8491;</td></tr>
--->
+<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=FGP:2-AMINO-3-HYDROXY-3-PHOSPHONOOXY-PROPIONIC+ACID'>FGP</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
-{{STRUCTURE_1n2l|  PDB=1n2l  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1n2l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n2l OCA], [https://pdbe.org/1n2l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1n2l RCSB], [https://www.ebi.ac.uk/pdbsum/1n2l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1n2l ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/ARSA_HUMAN ARSA_HUMAN] Defects in ARSA are a cause of leukodystrophy metachromatic (MLD) [MIM:[https://omim.org/entry/250100 250100]. MLD is a disease due to a lysosomal storage defect. It is characterized by intralysosomal storage of cerebroside-3-sulfate in neural and non-neural tissues, with a diffuse loss of myelin in the central nervous system. Progressive demyelination causes a variety of neurological symptoms, including gait disturbances, ataxias, optical atrophy, dementia, seizures, and spastic tetraparesis. Three forms of the disease can be distinguished according to the age at onset: late-infantile, juvenile and adult.<ref>PMID:1673291</ref> <ref>PMID:1678251</ref> <ref>PMID:1670590</ref> <ref>PMID:1353340</ref> <ref>PMID:8101038</ref> <ref>PMID:8101083</ref> <ref>PMID:8095918</ref> <ref>PMID:7902317</ref> <ref>PMID:7906588</ref> <ref>PMID:8104633</ref> <ref>PMID:7909527</ref> <ref>PMID:7825603</ref> <ref>PMID:7860068</ref> <ref>PMID:7581401</ref> <ref>PMID:8891236</ref> <ref>PMID:9272717</ref> <ref>PMID:9090526</ref> <ref>PMID:9490297</ref> <ref>PMID:9600244</ref> <ref>PMID:9452102</ref> <ref>PMID:9819708</ref> <ref>PMID:10220151</ref> <ref>PMID:10477432</ref> <ref>PMID:10533072</ref> <ref>PMID:10381328</ref> <ref>PMID:10751093</ref> <ref>PMID:11061266</ref> <ref>PMID:11020646</ref> <ref>PMID:11456299</ref> <ref>PMID:11941485</ref> <ref>PMID:12503099</ref> <ref>PMID:12788103</ref> <ref>PMID:14517960</ref> <ref>PMID:14680985</ref> <ref>PMID:15326627</ref> <ref>PMID:15026521</ref> <ref>PMID:15710861</ref> <ref>PMID:18693274</ref> <ref>PMID:19606494</ref> <ref>PMID:20339381</ref> <ref>PMID:21265945</ref>   Arylsulfatase A activity is defective in multiple sulfatase deficiency (MSD) [MIM:[https://omim.org/entry/272200 272200]. 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. Note=Arylsulfatase A activity is impaired in multiple sulfatase deficiency due to mutations in SUMF1. SUMF1 mutations result in defective post-translational modification of ARSA at residue Cys-69 that is not converted to 3-oxoalanine.<ref>PMID:7628016</ref> <ref>PMID:15146462</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/ARSA_HUMAN ARSA_HUMAN] Hydrolyzes cerebroside sulfate.
+== 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/n2/1n2l_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=1n2l ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The structures of human arylsulfatase A crystals soaked in solutions containing 4-methylumbelliferyl phosphate and O-phospho-DL-tyrosine have been determined at 2.7- and 3.2-A resolution, respectively. The formylglycine in position 69, a residue crucial for catalytic activity, was unambiguously identified in both structures as forming a covalent bond to the phosphate moiety. A hydroxyl group is present at the Cbeta of residue 69 and the formation of one out of two possible stereomeric forms is strongly favoured. The structures confirm the importance of the gem-diol intermediate in the arylsulfatase's catalytic mechanism. The presence of an apparently stable covalent bond is consistent with the weak phosphatase activity observed for human arylsulfatase A. The structures of the complexes suggest that phosphate ions and phosphate esters inhibit arylsulfatase in non-covalent and covalent modes, respectively. The metal ion present in the active site of arylsulfatase A isolated from human placenta is Ca(2+) and not Mg(2+) as was found in the structure of the recombinant enzyme.
-===Crystal structure of a covalent intermediate of endogenous human arylsulfatase A===
+Crystal structure of a covalent intermediate of endogenous human arylsulfatase A.,Chruszcz M, Laidler P, Monkiewicz M, Ortlund E, Lebioda L, Lewinski K J Inorg Biochem. 2003 Aug 1;96(2-3):386-92. PMID:12888274<ref>PMID:12888274</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 1n2l" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_12888274}}, adds the Publication Abstract to the page
+*[[Sulfatase 3D structures|Sulfatase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 12888274 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_12888274}}
+__TOC__
+</StructureSection>
-==About this Structure==
-N2L 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=1N2L OCA].
-==Reference==
-Crystal structure of a covalent intermediate of endogenous human arylsulfatase A., Chruszcz M, Laidler P, Monkiewicz M, Ortlund E, Lebioda L, Lewinski K, J Inorg Biochem. 2003 Aug 1;96(2-3):386-92. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12888274 12888274]
-[[Category: Cerebroside-sulfatase]]
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Chruszcz, M.]]
+[[Category: Chruszcz M]]
-[[Category: Laidler, P.]]
+[[Category: Laidler P]]
-[[Category: Lebioda, L.]]
+[[Category: Lebioda L]]
-[[Category: Lewinski, K.]]
+[[Category: Lewinski K]]
-[[Category: Monkiewicz, M.]]
+[[Category: Monkiewicz M]]
-[[Category: Ortlund, E.]]
+[[Category: Ortlund E]]
-[[Category: Hydrolase]]
-[[Category: Inhibition]]
-[[Category: Lysosomal enzyme]]
-[[Category: Metal ion]]
-[[Category: Modified formylglycine]]
-[[Category: Phosphate ester hydrolysis]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 21:27:35 2008''