3GVQ

UROD single-chain dimer

3GVQ の概要

• エントリーDOI: 10.2210/pdb3gvq/pdb
• 関連するPDBエントリー: 1uro 3GVR 3GVV 3GVW
• 分子名称: Uroporphyrinogen decarboxylase (2 entities in total)
• 機能のキーワード: heme, uroporphyrinogen, decarboxylase, alpha-8-beta-8 barrel, lyase, acetylation, cytoplasm, disease mutation, heme biosynthesis, phosphoprotein, porphyrin biosynthesis
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm: P06132
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 40831.77

構造登録者

Hill, C.P.,Phillips, J.D.,Warby, C.,Whitby, F.G.,Kushner, J.P. (登録日: 2009-03-31, 公開日: 2009-07-07, 最終更新日: 2023-09-06)

主引用文献

Phillips, J.D.,Warby, C.A.,Whitby, F.G.,Kushner, J.P.,Hill, C.P.
Substrate shuttling between active sites of uroporphyrinogen decarboxylase is not required to generate coproporphyrinogen.
J.Mol.Biol., 389:306-314, 2009

PubMed Abstract: Uroporphyrinogen decarboxylase (URO-D; EC 4.1.1.37), the fifth enzyme of the heme biosynthetic pathway, is required for the production of heme, vitamin B12, siroheme, and chlorophyll precursors. URO-D catalyzes the sequential decarboxylation of four acetate side chains in the pyrrole groups of uroporphyrinogen to produce coproporphyrinogen. URO-D is a stable homodimer, with the active-site clefts of the two subunits adjacent to each other. It has been hypothesized that the two catalytic centers interact functionally, perhaps by shuttling of reaction intermediates between subunits. We tested this hypothesis by construction of a single-chain protein (single-chain URO-D) in which the two subunits were connected by a flexible linker. The crystal structure of this protein was shown to be superimposable with wild-type activity and to have comparable catalytic activity. Mutations that impaired one or the other of the two active sites of single-chain URO-D resulted in approximately half of wild-type activity. The distributions of reaction intermediates were the same for mutant and wild-type sequences and were unaltered in a competition experiment using I and III isomer substrates. These observations indicate that communication between active sites is not required for enzyme function and suggest that the dimeric structure of URO-D is required to achieve conformational stability and to create a large active-site cleft.

PubMed: 19362562
DOI: 10.1016/j.jmb.2009.04.013

実験手法

X-RAY DIFFRACTION (2.1 Å)