5z5m

Crystal structure of (S)-allantoin synthase

spinqualitylabelsall models 5z5m, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5z5m is a 4 chain structure with sequence from Phaeodactylum tricornutum CCAP 1055/1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.85Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function B7GAW6_PHATC Catalyzes the stereoselective decarboxylation of 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (OHCU) to (S)-allantoin.[ARBA:ARBA00002506] Publication Abstract from PubMed Humans have lost the ability to convert urate into the more soluble allantoin with the evolutionary inactivation of three enzymes of the uricolytic pathway. Restoration of this function through enzyme replacement therapy can treat severe hyperuricemia and Lesch-Nyhan disease. Through a genomic exploration of natural gene fusions, we found that plants and diatoms independently evolved a fusion protein (allantoin synthase) complementing two human pseudogenes. The 1.85-A-resolution crystal structure of allantoin synthase from the diatom Phaeodactylum tricornutum provides a rationale for the domain combinations observed in the metabolic pathway, suggesting that quaternary structure is key to the evolutionary success of protein domain fusions. Polyethylene glycol (PEG) conjugation experiments indicate that a PEG-modified form of the natural fusion protein provides advantages over separate enzymes in terms of activity maintenance and manufacturing of the bioconjugate. These results suggest that the combination of different activities in a single molecular unit can simplify the production and chemical modification of recombinant proteins for multifunctional enzyme therapy. Diatom Allantoin Synthase Provides Structural Insights into Natural Fusion Protein Therapeutics.,Oh J, Liuzzi A, Ronda L, Marchetti M, Corsini R, Folli C, Bettati S, Rhee S, Percudani R ACS Chem Biol. 2018 Aug 17;13(8):2237-2246. doi: 10.1021/acschembio.8b00404. Epub, 2018 Jun 28. PMID:29874034 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA