View source for 4kgl


==Crystal structure of human alpha-L-iduronidase complex with [2R,3R,4R,5S]-2-carboxy-3,4,5-trihydroxy-piperidine==
<StructureSection load='4kgl' size='340' side='right'caption='[[4kgl]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4kgl]] is a 2 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=4KGL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KGL 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]] 2.701&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IDJ:(2R,3R,4R,5S)-3,4,5-TRIHYDROXYPIPERIDINE-2-CARBOXYLIC+ACID'>IDJ</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</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=4kgl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kgl OCA], [https://pdbe.org/4kgl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kgl RCSB], [https://www.ebi.ac.uk/pdbsum/4kgl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kgl ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/IDUA_HUMAN IDUA_HUMAN] Hurler-Scheie syndrome;Hurler syndrome;Scheie syndrome. Defects in IDUA are the cause of mucopolysaccharidosis type 1H (MPS1H) [MIM:[https://omim.org/entry/607014 607014]; also known as Hurler syndrome. MPS1H is a severe form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. Patients with MPS1H usually present, within the first year of life, a combination of hepatosplenomegaly, skeletal deformities, corneal clouding and severe mental retardation. Obstructive airways disease, respiratory infection and cardiac complications usually result in death before 10 years of age.<ref>PMID:8019563</ref> <ref>PMID:8401515</ref> <ref>PMID:8328452</ref> <ref>PMID:1301941</ref> <ref>PMID:7951228</ref> <ref>PMID:7550232</ref> <ref>PMID:7550242</ref> <ref>PMID:1946389</ref> <ref>PMID:10466419</ref> <ref>PMID:10735634</ref> <ref>PMID:12559846</ref> <ref>PMID:15300847</ref> <ref>PMID:21394825</ref>   Defects in IDUA are the cause of mucopolysaccharidosis type 1H/S (MPS1H/S) [MIM:[https://omim.org/entry/607015 607015]; also known as Hurler-Scheie syndrome. MPS1H/S is a form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. MPS1H/S represents an intermediate phenotype of the MPS1 clinical spectrum. It is characterized by relatively little neurological involvement, but most of the somatic symptoms described for severe MPS1 develop in the early to mid-teens, causing considerable loss of mobility.  Defects in IDUA are the cause of mucopolysaccharidosis type 1S (MPS1S) [MIM:[https://omim.org/entry/607016 607016]; also known as Scheie syndrome. MPS1S is a mild form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. Patients with MPS1S may have little or no neurological involvement, normal stature and life span, but present development of joints stiffness, mild hepatosplenomegaly, aortic valve disease and corneal clouding.
== Function ==
[https://www.uniprot.org/uniprot/IDUA_HUMAN IDUA_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Mucopolysaccharidosis type I (MPS I), caused by mutations in the gene encoding alpha-L-iduronidase (IDUA), is one of approximately 70 genetic disorders collectively known as the lysosomal storage diseases. To gain insight into the basis for MPS I, we crystallized human IDUA produced in an Arabidopsis thaliana cgl mutant. IDUA consists of a TIM barrel domain containing the catalytic site, a beta-sandwich domain and a fibronectin-like domain. Structures of IDUA bound to iduronate analogs illustrate the Michaelis complex and reveal a 2,5B conformation in the glycosyl-enzyme intermediate, which suggest a retaining double displacement reaction involving the nucleophilic Glu299 and the general acid/base Glu182. Unexpectedly, the N-glycan attached to Asn372 interacts with iduronate analogs in the active site and is required for enzymatic activity. Finally, these IDUA structures and biochemical analysis of the disease-relevant P533R mutation have enabled us to correlate the effects of mutations in IDUA to clinical phenotypes.

Insights into mucopolysaccharidosis I from the structure and action of alpha-L-iduronidase.,Bie H, Yin J, He X, Kermode AR, Goddard-Borger ED, Withers SG, James MN Nat Chem Biol. 2013 Sep 11. doi: 10.1038/nchembio.1357. PMID:24036510<ref>PMID:24036510</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4kgl" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bie H]]
[[Category: Goddard-Borger ED]]
[[Category: He X]]
[[Category: James MNG]]
[[Category: Kermode AR]]
[[Category: Withers SG]]
[[Category: Yin J]]