View source for 9avs


==Human alpha-galactosidase A in complex with saposin B==
<StructureSection load='9avs' size='340' side='right'caption='[[9avs]], [[Resolution|resolution]] 3.53&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9avs]] is a 3 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=9AVS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9AVS 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]] 3.53&#8491;</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=9avs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9avs OCA], [https://pdbe.org/9avs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9avs RCSB], [https://www.ebi.ac.uk/pdbsum/9avs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9avs ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/AGAL_HUMAN AGAL_HUMAN] Defects in GLA are the cause of Fabry disease (FD) [MIM:[https://omim.org/entry/301500 301500]. FD is a rare X-linked sphingolipidosis disease where glycolipid accumulates in many tissues. The disease consists of an inborn error of glycosphingolipid catabolism. FD patients show systemic accumulation of globotriaoslyceramide (Gb3) and related glycosphingolipids in the plasma and cellular lysosomes throughout the body. Clinical recognition in males results from characteristic skin lesions (angiokeratomas) over the lower trunk. Patients may show ocular deposits, febrile episodes, and burning pain in the extremities. Death results from renal failure, cardiac or cerebral complications of hypertension or other vascular disease. Heterozygous females may exhibit the disorder in an attenuated form, they are more likely to show corneal opacities.<ref>PMID:2152885</ref> <ref>PMID:1846223</ref> <ref>PMID:2171331</ref> <ref>PMID:2539398</ref> <ref>PMID:1315715</ref> <ref>PMID:7504405</ref> <ref>PMID:8395937</ref> <ref>PMID:8069316</ref> <ref>PMID:7531540</ref> <ref>PMID:7575533</ref> <ref>PMID:7759078</ref> <ref>PMID:7599642</ref> <ref>PMID:7596372</ref> <ref>PMID:8738659</ref> <ref>PMID:8875188</ref> <ref>PMID:8834244</ref> <ref>PMID:8931708</ref> <ref>PMID:8807334</ref> <ref>PMID:8863162</ref> <ref>PMID:9105656</ref> <ref>PMID:9100224</ref> <ref>PMID:9554750</ref> <ref>PMID:9452068</ref> <ref>PMID:9452090</ref> <ref>PMID:9452111</ref> <ref>PMID:10208848</ref> <ref>PMID:10090526</ref> <ref>PMID:10838196</ref> <ref>PMID:10666480</ref> <ref>PMID:11076046</ref> <ref>PMID:10916280</ref> <ref>PMID:11295840</ref> <ref>PMID:11668641</ref> <ref>PMID:11889412</ref> <ref>PMID:12694230</ref> <ref>PMID:12786754</ref> <ref>PMID:15162124</ref> <ref>PMID:15712228</ref> <ref>PMID:16533976</ref> <ref>PMID:19621417</ref> 
== Function ==
[https://www.uniprot.org/uniprot/AGAL_HUMAN AGAL_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Sphingolipid activator protein B (saposin B; SapB) is an essential activator of globotriaosylceramide (Gb3) catabolism by alpha-galactosidase A. However, the manner by which SapB stimulates alpha-galactosidase A activity remains unknown. To uncover the molecular mechanism of SapB presenting Gb3 to alpha-galactosidase A, we subjected the fluorescent substrate globotriaosylceramide-nitrobenzoxidazole (Gb3-NBD) to a series of biochemical and structural assays involving SapB. First, we showed that SapB stably binds Gb3-NBD using a fluorescence equilibrium binding assay, isolates Gb3-NBD from micelles, and facilitates alpha-galactosidase A cleavage of Gb3-NBD in vitro. Second, we crystallized SapB in the presence of Gb3-NBD and validated the ligand-bound assembly. Third, we captured transient interactions between SapB and alpha-galactosidase A by chemical cross-linking. Finally, we determined the crystal structure of SapB bound to alpha-galactosidase A. These findings establish general principles for molecular recognition in saposin:hydrolase complexes and highlight the utility of NBD reporter lipids in saposin biochemistry and structural biology.

Human Saposin B Ligand Binding and Presentation to alpha-Galactosidase A.,Sawyer TK, Aral E, Staros JV, Bobst CE, Garman SC bioRxiv [Preprint]. 2024 Apr 4:2024.04.04.584535. doi: 10.1101/2024.04.04.584535. PMID:38617236<ref>PMID:38617236</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9avs" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Garman SC]]
[[Category: Sawyer TK]]