4UEX
Structure of human Saposin A at lysosomal pH
Summary for 4UEX
| Entry DOI | 10.2210/pdb4uex/pdb |
| Descriptor | PROSAPOSIN (2 entities in total) |
| Functional Keywords | lipid binding protein, saposin a, saposin, sap, lipid transfer protein, sphingolipid activator protein |
| Biological source | HOMO SAPIENS (HUMAN) |
| Total number of polymer chains | 2 |
| Total formula weight | 18605.56 |
| Authors | Hill, C.H.,Read, R.J.,Deane, J.E. (deposition date: 2014-12-20, release date: 2015-07-15, Last modification date: 2024-11-13) |
| Primary citation | Hill, C.H.,Read, R.J.,Deane, J.E. Structure of Human Saposin a at Lysosomal Ph. Acta Crystallogr.,Sect.D, 71:895-, 2015 Cited by PubMed Abstract: The saposins are essential cofactors for the normal lysosomal degradation of complex glycosphingolipids by acid hydrolase enzymes; defects in either saposin or hydrolase function lead to severe metabolic diseases. Saposin A (SapA) activates the enzyme β-galactocerebrosidase (GALC), which catalyzes the breakdown of β-D-galactocerebroside, the principal lipid component of myelin. SapA is known to bind lipids and detergents in a pH-dependent manner; this is accompanied by a striking transition from a `closed' to an `open' conformation. However, previous structures were determined at non-lysosomal pH. This work describes a 1.8 Å resolution X-ray crystal structure determined at the physiologically relevant lysosomal pH 4.8. In the absence of lipid or detergent at pH 4.8, SapA is observeed to adopt a conformation closely resembling the previously determined `closed' conformation, showing that pH alone is not sufficient for the transition to the `open' conformation. Structural alignments reveal small conformational changes, highlighting regions of flexibility. PubMed: 26144235DOI: 10.1107/S2053230X15008584 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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