Structural highlights
6srf 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.
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| Method: | X-ray diffraction, Resolution 1.847Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
PEPD_HUMAN Defects in PEPD are a cause of prolidase deficiency (PD) [MIM:170100. Prolidase deficiency is an autosomal recessive disorder associated with iminodipeptiduria. The clinical phenotype includes skin ulcers, mental retardation, recurrent infections, and a characteristic facies. These features, however are incompletely penetrant and highly variable in both age of onset and severity. There is a tight linkage between the polymorphisms of prolidase and the myotonic dystrophy trait.[1] [2] [3] [4]
Function
PEPD_HUMAN Splits dipeptides with a prolyl or hydroxyprolyl residue in the C-terminal position. Plays an important role in collagen metabolism because the high level of iminoacids in collagen.
Publication Abstract from PubMed
Prolidase catalyzes the cleavage of dipeptides containing proline on their C terminus. The reduction in prolidase activity is the cause of a rare disease named 'Prolidase Deficiency'. Local structural disorder was indicated as one of the causes for diminished prolidase activity. Previous studies showed that heat shock proteins can partially recover prolidase activity in vivo. To analyze this mechanism of enzymatic activity rescue, we compared the crystal structures of selected prolidase mutants expressed in the absence and in the presence of chaperones. Our results confirm that protein chaperones facilitate the formation of more ordered structures by their substrate protein. These results also suggest that the protein expression system needs to be considered as an important parameter in structural studies. DATABASES: The reported crystal structures and their associated structure factor amplitudes were deposited in the Protein Data Bank under the accession codes 6SRE, 6SRF, and 6SRG, respectively.
Co-expression with chaperones can affect protein 3D structure as exemplified by loss-of-function variants of human prolidase.,Wator E, Rutkiewicz M, Weiss MS, Wilk P FEBS Lett. 2020 Sep;594(18):3045-3056. doi: 10.1002/1873-3468.13877. Epub 2020, Jul 14. PMID:32598484[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tanoue A, Endo F, Kitano A, Matsuda I. A single nucleotide change in the prolidase gene in fibroblasts from two patients with polypeptide positive prolidase deficiency. Expression of the mutant enzyme in NIH 3T3 cells. J Clin Invest. 1990 Jul;86(1):351-5. PMID:2365824 doi:http://dx.doi.org/10.1172/JCI114708
- ↑ Ledoux P, Scriver C, Hechtman P. Four novel PEPD alleles causing prolidase deficiency. Am J Hum Genet. 1994 Jun;54(6):1014-21. PMID:8198124
- ↑ Ledoux P, Scriver CR, Hechtman P. Expression and molecular analysis of mutations in prolidase deficiency. Am J Hum Genet. 1996 Nov;59(5):1035-9. PMID:8900231
- ↑ Forlino A, Lupi A, Vaghi P, Icaro Cornaglia A, Calligaro A, Campari E, Cetta G. Mutation analysis of five new patients affected by prolidase deficiency: the lack of enzyme activity causes necrosis-like cell death in cultured fibroblasts. Hum Genet. 2002 Oct;111(4-5):314-22. Epub 2002 Aug 14. PMID:12384772 doi:10.1007/s00439-002-0792-5
- ↑ Wątor E, Rutkiewicz M, Weiss MS, Wilk P. Co-expression with chaperones can affect protein 3D structure as exemplified by loss-of-function variants of human prolidase. FEBS Lett. 2020 Sep;594(18):3045-3056. PMID:32598484 doi:10.1002/1873-3468.13877
