View source for 2pe4


==Structure of Human Hyaluronidase 1, a Hyaluronan Hydrolyzing Enzyme Involved in Tumor Growth and Angiogenesis==
<StructureSection load='2pe4' size='340' side='right'caption='[[2pe4]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2pe4]] 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=2PE4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PE4 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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=2pe4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pe4 OCA], [https://pdbe.org/2pe4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pe4 RCSB], [https://www.ebi.ac.uk/pdbsum/2pe4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pe4 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/HYAL1_HUMAN HYAL1_HUMAN] Defects in HYAL1 are the cause of mucopolysaccharidosis type 9 (MPS9) [MIM:[https://omim.org/entry/601492 601492]; also called hyaluronidase deficiency. MPS9 is a lysosomal storage disease characterized by high hyaluronan (HA) concentration in the serum. The clinical features are periarticular soft tissue masses, mild short stature and acetabular erosions, and absence of neurological or visceral involvement.<ref>PMID:10339581</ref> 
== Function ==
[https://www.uniprot.org/uniprot/HYAL1_HUMAN HYAL1_HUMAN] May have a role in promoting tumor progression. May block the TGFB1-enhanced cell growth.<ref>PMID:12084718</ref> 
== 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/pe/2pe4_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2pe4 ConSurf].
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== Publication Abstract from PubMed ==
Mammalian hyaluronidases hydrolyze hyaluronan, a polysaccharide of diverse physiological roles found in all tissues and body fluids. In addition to its function in normal cellular hyaluronan turnover, human hyaluronidase-1 is implicated in cancer proliferation, angiogenesis, and inflammatory diseases; its expression is up-regulated in advanced stages of bladder cancer, whereas the expression of the alternative splice-variants is down-regulated. The crystal structure reveals a molecule composed of two closely associated domains: a catalytic domain that adopts a distorted (beta/alpha)8 barrel resembling that of bee venom hyaluronidase, and a novel, EGF-like domain, characteristic of involvement in protein-protein interactions and regulatory processes. The structure shows that the fold of this unique EGF-like domain is intact in four alternative splice-variants, whereas the catalytic domain is likely to be unfolded. Thus, these variants may function by competing with the full-length enzyme for the putative protein partner and regulating enzymatic activity in healthy cells.

Structure of human hyaluronidase-1, a hyaluronan hydrolyzing enzyme involved in tumor growth and angiogenesis.,Chao KL, Muthukumar L, Herzberg O Biochemistry. 2007 Jun 12;46(23):6911-20. Epub 2007 May 16. PMID:17503783<ref>PMID:17503783</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2pe4" style="background-color:#fffaf0;"></div>

==See Also==
*[[Hyaluronidase 3D structures|Hyaluronidase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chao KL]]
[[Category: Herzberg O]]