4E1O

Human histidine decarboxylase complex with Histidine methyl ester (HME)

4E1O の概要

• エントリーDOI: 10.2210/pdb4e1o/pdb
• 分子名称: Histidine decarboxylase, PYRIDOXAL-5'-PHOSPHATE, HISTIDINE-METHYL-ESTER, ... (4 entities in total)
• 機能のキーワード: histidine decarboxylase, lyase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 328389.02

構造登録者

Komori, H.,Nitta, Y.,Ueno, H.,Higuchi, Y. (登録日: 2012-03-06, 公開日: 2012-07-18, 最終更新日: 2023-11-15)

主引用文献

Komori, H.,Nitta, Y.,Ueno, H.,Higuchi, Y.
Structural study reveals that Ser-354 determines substrate specificity on human histidine decarboxylase
J.Biol.Chem., 287:29175-29183, 2012

PubMed Abstract: Histamine is an important chemical mediator for a wide variety of physiological reactions. L-histidine decarboxylase (HDC) is the primary enzyme responsible for histamine synthesis and produces histamine from histidine in a one-step reaction. In this study, we determined the crystal structure of human HDC (hHDC) complexed with the inhibitor histidine methyl ester. This structure shows the detailed features of the pyridoxal-5'-phosphate inhibitor adduct (external aldimine) at the active site of HDC. Moreover, a comparison of the structures of hHDC and aromatic L-amino acid (L-DOPA) decarboxylase showed that Ser-354 was a key residue for substrate specificity. The S354G mutation at the active site enlarged the size of the hHDC substrate-binding pocket and resulted in a decreased affinity for histidine, but an acquired ability to bind and act on L-DOPA as a substrate. These data provide insight into the molecular basis of substrate recognition among the group II pyridoxal-5'-phosphate-dependent decarboxylases.

PubMed: 22767596
DOI: 10.1074/jbc.M112.381897

実験手法

X-RAY DIFFRACTION (1.8 Å)