4zdl

The crystal structure of the T325S mutant of the human holo SepSecS

spinqualitylabelsall models 4zdl, resolution 2.26Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4zdl is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.26Å Ligands: FLC, PLR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SPCS_HUMAN Publication Abstract from PubMed Selenocysteine synthase (SepSecS) catalyzes the terminal reaction of selenocysteine, and is vital for human selenoproteome integrity. Autosomal recessive inheritance of mutations in SepSecS-Ala239Thr, Thr325Ser, Tyr334Cys and Tyr429*-induced severe, early-onset, neurological disorders in distinct human populations. Although harboring different mutant alleles, patients presented remarkably similar phenotypes typified by cerebellar and cerebral atrophy, seizures, irritability, ataxia, and extreme spasticity. However, it has remained unclear how these genetic alterations affected the structure of SepSecS and subsequently elicited the development of a neurological pathology. Herein, our biophysical and structural characterization demonstrates that, with the exception of Tyr429*, pathogenic mutations decrease protein stability and trigger protein misfolding. We propose that the reduced stability and increased propensity towards misfolding are the main causes for the loss of SepSecS activity in afflicted patients, and that these factors contribute to disease progression. We also suggest that misfolding of enzymes regulating protein synthesis should be considered in the diagnosis and study of childhood neurological disorders. Structural basis for early-onset neurological disorders caused by mutations in human selenocysteine synthase.,Puppala AK, French RL, Matthies D, Baxa U, Subramaniam S, Simonovic M Sci Rep. 2016 Aug 31;6:32563. doi: 10.1038/srep32563. PMID:27576344 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Selenocysteine synthase

Proteopedia Page Contributors and Editors (what is this?)

OCA