1TOH

TYROSINE HYDROXYLASE CATALYTIC AND TETRAMERIZATION DOMAINS FROM RAT

1TOH の概要

• エントリーDOI: 10.2210/pdb1toh/pdb
• 分子名称: TYROSINE HYDROXYLASE, FE (III) ION (3 entities in total)
• 機能のキーワード: hydroxylase, neurotransmitter biosynthesis, non-heme iron, pterin co-substrate
• 由来する生物種: Rattus norvegicus (Norway rat)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 39329.93

構造登録者

Goodwill, K.E.,Sabatier, C.,Stevens, R.C. (登録日: 1997-06-04, 公開日: 1998-06-03, 最終更新日: 2024-02-14)

主引用文献

Goodwill, K.E.,Sabatier, C.,Marks, C.,Raag, R.,Fitzpatrick, P.F.,Stevens, R.C.
Crystal structure of tyrosine hydroxylase at 2.3 A and its implications for inherited neurodegenerative diseases.
Nat.Struct.Biol., 4:578-585, 1997

PubMed Abstract: Tyrosine hydroxylase (TyrOH) catalyzes the conversion of tyrosine to L-DOPA, the rate-limiting step in the biosynthesis of the catecholamines dopamine, adrenaline, and noradrenaline. TyrOH is highly homologous in terms of both protein sequence and catalytic mechanism to phenylalanine hydroxylase (PheOH) and tryptophan hydroxylase (TrpOH). The crystal structure of the catalytic and tetramerization domains of TyrOH reveals a novel alpha-helical basket holding the catalytic iron and a 40 A long anti-parallel coiled coil which forms the core of the tetramer. The catalytic iron is located 10 A below the enzyme surface in a 17 A deep active site pocket and is coordinated by the conserved residues His 331, His 336 and Glu 376. The structure provides a rationale for the effect of point mutations in TyrOH that cause L-DOPA responsive parkinsonism and Segawa's syndrome. The location of 112 different point mutations in PheOH that lead to phenylketonuria (PKU) are predicted based on the TyrOH structure.

PubMed: 9228951
DOI: 10.1038/nsb0797-578

実験手法

X-RAY DIFFRACTION (2.3 Å)