6h2q

Crystal Structure of Arg184Gln mutant of Human Prolidase with Mn ions and LeuPro ligand

spinqualitylabelsall models 6h2q, resolution 1.78Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6h2q 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 1.78Å Ligands: GOL, LEU, MN, PRO 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. 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 is a metallopeptidase that cleaves iminodipeptides containing a proline (Pro) or hydroxyproline (Hyp) residue at their C-terminal end. The disease prolidase deficiency (PD) is a rare recessive human disorder characterized by reduced prolidase activity. PD manifests itself by a wide range of severe clinical symptoms, most commonly as skin ulceration, recurrent infections of the respiratory tract, and mental retardation. Several mutations in the PEPD gene have been identified that are responsible for the loss or the reduction of prolidase activity. In contrast, the structural basis of enzyme inactivation has so far remained elusive. In this study, we present high resolution crystal structures of a number of human prolidase (HsProl) variants, in which single amino acids are either substituted by others or deleted. The observed implications of the mutations on the three-dimensional structure of HsProl are reported and discussed and related to their enzymatic activity. The resulting structures may be divided into four groups depending on the presumed effect of the corresponding mutations on the reaction mechanism. The four possible inactivation mechanisms, which could be elucidated, are disruption of the catalytic Mn2 (OH(-) )-center, introduction of chain disorder along with the displacement of important active site residues, rigidification of the active site, and flexibilization of the active site. DATABASE: All refined structure coordinates as well as the corresponding structure factor amplitudes have been deposited in the PDB under the accession numbers 5MBY, 5MBZ, 5MC0, 5MC1, 5MC2, 5MC3, 5MC4, 5MC5, 6H2P, 6H2Q. Structural basis for prolidase deficiency disease mechanisms.,Wilk P, Uehlein M, Piwowarczyk R, Dobbek H, Mueller U, Weiss MS FEBS J. 2018 Aug 1. doi: 10.1111/febs.14620. PMID:30066404 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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