5Z5M

Crystal structure of (S)-allantoin synthase

5Z5M の概要

• エントリーDOI: 10.2210/pdb5z5m/pdb
• 分子名称: Predicted protein (2 entities in total)
• 機能のキーワード: allantoin synthase, ohcu decarboxylase, hiu hydrolase, urate, lyase
• 由来する生物種: Phaeodactylum tricornutum CCAP 1055/1
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 131380.81

構造登録者

Oh, J.,Percudani, R.,Rhee, S. (登録日: 2018-01-18, 公開日: 2018-11-21, 最終更新日: 2023-11-22)

主引用文献

Oh, J.,Liuzzi, A.,Ronda, L.,Marchetti, M.,Corsini, R.,Folli, C.,Bettati, S.,Rhee, S.,Percudani, R.
Diatom Allantoin Synthase Provides Structural Insights into Natural Fusion Protein Therapeutics.
ACS Chem. Biol., 13:2237-2246, 2018

PubMed Abstract: 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-Å-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.

PubMed: 29874034
DOI: 10.1021/acschembio.8b00404

実験手法

X-RAY DIFFRACTION (1.85 Å)