Suppr超能文献

结构研究表明,丝氨酸 354 决定了人组氨酸脱羧酶的底物特异性。

Structural study reveals that Ser-354 determines substrate specificity on human histidine decarboxylase.

机构信息

Department of Life Science, Graduate School of Life Science, University of Hyogo, 3-2-1 Koto, Kamigori-cho, Ako-gun, Hyogo 678-1297, Japan.

出版信息

J Biol Chem. 2012 Aug 17;287(34):29175-83. doi: 10.1074/jbc.M112.381897. Epub 2012 Jul 5.

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.

摘要

组氨酸是多种生理反应的重要化学介质。L-组氨酸脱羧酶(HDC)是负责组氨酸合成的主要酶,它在一步反应中从组氨酸产生组氨酸。在这项研究中,我们确定了与人 HDC(hHDC)复合的抑制剂组氨酸甲酯的晶体结构。该结构显示了 HDC 活性位点处吡啶醛-5'-磷酸抑制剂加合物(外部醛亚胺)的详细特征。此外,hHDC 和芳香族 L-氨基酸(L-DOPA)脱羧酶结构的比较表明,Ser-354 是决定底物特异性的关键残基。活性位点的 S354G 突变增大了 hHDC 底物结合口袋的大小,导致对组氨酸的亲和力降低,但获得了结合和作用于 L-DOPA 作为底物的能力。这些数据提供了组 II 依赖吡啶醛-5'-磷酸的脱羧酶之间底物识别的分子基础的深入了解。

相似文献

1
Structural study reveals that Ser-354 determines substrate specificity on human histidine decarboxylase.
J Biol Chem. 2012 Aug 17;287(34):29175-83. doi: 10.1074/jbc.M112.381897. Epub 2012 Jul 5.
2
Inhibitory and structural studies of novel coenzyme-substrate analogs of human histidine decarboxylase.
FASEB J. 2008 Mar;22(3):890-7. doi: 10.1096/fj.07-9566com. Epub 2007 Oct 26.
3
Homology-based molecular modelling of PLP-dependent histidine decarboxylase from Mmorganella morganii.
Eur J Med Chem. 2000 Jun;35(6):567-76. doi: 10.1016/s0223-5234(00)00155-0.
4
A single amino acid substitution converts a histidine decarboxylase to an imidazole acetaldehyde synthase.
Arch Biochem Biophys. 2020 Oct 30;693:108551. doi: 10.1016/j.abb.2020.108551. Epub 2020 Aug 29.
9
pH-induced structural changes regulate histidine decarboxylase activity in Lactobacillus 30a.
J Mol Biol. 2001 Mar 2;306(4):727-32. doi: 10.1006/jmbi.2000.4430.

引用本文的文献

5
Histamine synthesis and transport are coupled in axon terminals via a dual quality control system.
EMBO J. 2024 Oct;43(20):4472-4491. doi: 10.1038/s44318-024-00223-0. Epub 2024 Sep 6.
6
Potential for host-symbiont communication via neurotransmitters and neuromodulators in an aneural animal, the marine sponge .
Front Neural Circuits. 2023 Sep 29;17:1250694. doi: 10.3389/fncir.2023.1250694. eCollection 2023.
7
Aromatic L-amino acid decarboxylases: mechanistic features and microbial applications.
Appl Microbiol Biotechnol. 2022 Jun;106(12):4445-4458. doi: 10.1007/s00253-022-12028-4. Epub 2022 Jun 28.

本文引用的文献

1
Processing of X-ray diffraction data collected in oscillation mode.
Methods Enzymol. 1997;276:307-26. doi: 10.1016/S0076-6879(97)76066-X.
2
Purification, crystallization and preliminary X-ray analysis of human histidine decarboxylase.
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 Jun 1;68(Pt 6):675-7. doi: 10.1107/S1744309112015692. Epub 2012 May 23.
3
Histamine in neurotransmission and brain diseases.
Adv Exp Med Biol. 2010;709:95-107. doi: 10.1007/978-1-4419-8056-4_10.
4
Molecular insights into the pathogenicity of variants associated with the aromatic amino acid decarboxylase deficiency.
J Inherit Metab Dis. 2011 Dec;34(6):1213-24. doi: 10.1007/s10545-011-9340-6. Epub 2011 May 4.
5
L-histidine decarboxylase and Tourette's syndrome.
N Engl J Med. 2010 May 20;362(20):1901-8. doi: 10.1056/NEJMoa0907006. Epub 2010 May 5.
7
The development of allergic inflammation.
Nature. 2008 Jul 24;454(7203):445-54. doi: 10.1038/nature07204.
9
Analysis of the decarboxylation step in mammalian histidine decarboxylase. A computational study.
J Biol Chem. 2008 May 2;283(18):12393-401. doi: 10.1074/jbc.M707434200. Epub 2008 Feb 29.
10
Inhibitory and structural studies of novel coenzyme-substrate analogs of human histidine decarboxylase.
FASEB J. 2008 Mar;22(3):890-7. doi: 10.1096/fj.07-9566com. Epub 2007 Oct 26.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验