6ZSP

Human serine racemase bound to ATP and malonate.

これはPDB形式変換不可エントリーです。

6ZSP の概要

• エントリーDOI: 10.2210/pdb6zsp/pdb
• 分子名称: Serine racemase, IMIDAZOLE, MAGNESIUM ION, ... (8 entities in total)
• 機能のキーワード: plp-dependent, d-serine, atp, forebrain, isomerase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 77565.57

構造登録者

Koulouris, C.R.,Bax, B.D.,Roe, S.M.,Atack, J.R. (登録日: 2020-07-16, 公開日: 2021-03-03, 最終更新日: 2024-01-31)

主引用文献

Koulouris, C.R.,Gardiner, S.E.,Harris, T.K.,Elvers, K.T.,Mark Roe, S.,Gillespie, J.A.,Ward, S.E.,Grubisha, O.,Nicholls, R.A.,Atack, J.R.,Bax, B.D.
Tyrosine 121 moves revealing a ligandable pocket that couples catalysis to ATP-binding in serine racemase.
Commun Biol, 5:346-346, 2022

PubMed Abstract: Human serine racemase (hSR) catalyses racemisation of L-serine to D-serine, the latter of which is a co-agonist of the NMDA subtype of glutamate receptors that are important in synaptic plasticity, learning and memory. In a 'closed' hSR structure containing the allosteric activator ATP, the inhibitor malonate is enclosed between the large and small domains while ATP is distal to the active site, residing at the dimer interface with the Tyr121 hydroxyl group contacting the α-phosphate of ATP. In contrast, in 'open' hSR structures, Tyr121 sits in the core of the small domain with its hydroxyl contacting the key catalytic residue Ser84. The ability to regulate SR activity by flipping Tyr121 from the core of the small domain to the dimer interface appears to have evolved in animals with a CNS. Multiple X-ray crystallographic enzyme-fragment structures show Tyr121 flipped out of its pocket in the core of the small domain. Data suggest that this ligandable pocket could be targeted by molecules that inhibit enzyme activity.

PubMed: 35410329
DOI: 10.1038/s42003-022-03264-5

実験手法

X-RAY DIFFRACTION (1.6 Å)