Structural basis of the γ-lactone-ring formation in ascorbic acid biosynthesis by the senescence marker protein-30/gluconolactonase.

The senescence marker protein-30 (SMP30), which is also called regucalcin, exhibits gluconolactonase (GNL) activity. Biochemical and biological analyses revealed that SMP30/GNL catalyzes formation of the γ-lactone-ring of L-gulonate in the ascorbic acid biosynthesis pathway. The molecular basis of t...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Shingo Aizawa, Miki Senda, Ayaka Harada, Naoki Maruyama, Tetsuo Ishida, Toshiro Aigaki, Akihito Ishigami, Toshiya Senda
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a322213e27734ed3be756a0637318a3a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a322213e27734ed3be756a0637318a3a
record_format	dspace
spelling	oai:doaj.org-article:a322213e27734ed3be756a0637318a3a2021-11-18T08:00:40ZStructural basis of the γ-lactone-ring formation in ascorbic acid biosynthesis by the senescence marker protein-30/gluconolactonase.1932-620310.1371/journal.pone.0053706https://doaj.org/article/a322213e27734ed3be756a0637318a3a2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23349732/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The senescence marker protein-30 (SMP30), which is also called regucalcin, exhibits gluconolactonase (GNL) activity. Biochemical and biological analyses revealed that SMP30/GNL catalyzes formation of the γ-lactone-ring of L-gulonate in the ascorbic acid biosynthesis pathway. The molecular basis of the γ-lactone formation, however, remains elusive due to the lack of structural information on SMP30/GNL in complex with its substrate. Here, we report the crystal structures of mouse SMP30/GNL and its complex with xylitol, a substrate analogue, and those with 1,5-anhydro-D-glucitol and D-glucose, product analogues. Comparison of the crystal structure of mouse SMP30/GNL with other related enzymes has revealed unique characteristics of mouse SMP30/GNL. First, the substrate-binding pocket of mouse SMP30/GNL is designed to specifically recognize monosaccharide molecules. The divalent metal ion in the active site and polar residues lining the substrate-binding cavity interact with hydroxyl groups of substrate/product analogues. Second, in mouse SMP30/GNL, a lid loop covering the substrate-binding cavity seems to hamper the binding of L-gulonate in an extended (or all-trans) conformation; L-gulonate seems to bind to the active site in a folded conformation. In contrast, the substrate-binding cavities of the other related enzymes are open to the solvent and do not have a cover. This structural feature of mouse SMP30/GNL seems to facilitate the γ-lactone-ring formation.Shingo AizawaMiki SendaAyaka HaradaNaoki MaruyamaTetsuo IshidaToshiro AigakiAkihito IshigamiToshiya SendaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e53706 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shingo Aizawa Miki Senda Ayaka Harada Naoki Maruyama Tetsuo Ishida Toshiro Aigaki Akihito Ishigami Toshiya Senda Structural basis of the γ-lactone-ring formation in ascorbic acid biosynthesis by the senescence marker protein-30/gluconolactonase.
description	The senescence marker protein-30 (SMP30), which is also called regucalcin, exhibits gluconolactonase (GNL) activity. Biochemical and biological analyses revealed that SMP30/GNL catalyzes formation of the γ-lactone-ring of L-gulonate in the ascorbic acid biosynthesis pathway. The molecular basis of the γ-lactone formation, however, remains elusive due to the lack of structural information on SMP30/GNL in complex with its substrate. Here, we report the crystal structures of mouse SMP30/GNL and its complex with xylitol, a substrate analogue, and those with 1,5-anhydro-D-glucitol and D-glucose, product analogues. Comparison of the crystal structure of mouse SMP30/GNL with other related enzymes has revealed unique characteristics of mouse SMP30/GNL. First, the substrate-binding pocket of mouse SMP30/GNL is designed to specifically recognize monosaccharide molecules. The divalent metal ion in the active site and polar residues lining the substrate-binding cavity interact with hydroxyl groups of substrate/product analogues. Second, in mouse SMP30/GNL, a lid loop covering the substrate-binding cavity seems to hamper the binding of L-gulonate in an extended (or all-trans) conformation; L-gulonate seems to bind to the active site in a folded conformation. In contrast, the substrate-binding cavities of the other related enzymes are open to the solvent and do not have a cover. This structural feature of mouse SMP30/GNL seems to facilitate the γ-lactone-ring formation.
format	article
author	Shingo Aizawa Miki Senda Ayaka Harada Naoki Maruyama Tetsuo Ishida Toshiro Aigaki Akihito Ishigami Toshiya Senda
author_facet	Shingo Aizawa Miki Senda Ayaka Harada Naoki Maruyama Tetsuo Ishida Toshiro Aigaki Akihito Ishigami Toshiya Senda
author_sort	Shingo Aizawa
title	Structural basis of the γ-lactone-ring formation in ascorbic acid biosynthesis by the senescence marker protein-30/gluconolactonase.
title_short	Structural basis of the γ-lactone-ring formation in ascorbic acid biosynthesis by the senescence marker protein-30/gluconolactonase.
title_full	Structural basis of the γ-lactone-ring formation in ascorbic acid biosynthesis by the senescence marker protein-30/gluconolactonase.
title_fullStr	Structural basis of the γ-lactone-ring formation in ascorbic acid biosynthesis by the senescence marker protein-30/gluconolactonase.
title_full_unstemmed	Structural basis of the γ-lactone-ring formation in ascorbic acid biosynthesis by the senescence marker protein-30/gluconolactonase.
title_sort	structural basis of the γ-lactone-ring formation in ascorbic acid biosynthesis by the senescence marker protein-30/gluconolactonase.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/a322213e27734ed3be756a0637318a3a
work_keys_str_mv	AT shingoaizawa structuralbasisoftheglactoneringformationinascorbicacidbiosynthesisbythesenescencemarkerprotein30gluconolactonase AT mikisenda structuralbasisoftheglactoneringformationinascorbicacidbiosynthesisbythesenescencemarkerprotein30gluconolactonase AT ayakaharada structuralbasisoftheglactoneringformationinascorbicacidbiosynthesisbythesenescencemarkerprotein30gluconolactonase AT naokimaruyama structuralbasisoftheglactoneringformationinascorbicacidbiosynthesisbythesenescencemarkerprotein30gluconolactonase AT tetsuoishida structuralbasisoftheglactoneringformationinascorbicacidbiosynthesisbythesenescencemarkerprotein30gluconolactonase AT toshiroaigaki structuralbasisoftheglactoneringformationinascorbicacidbiosynthesisbythesenescencemarkerprotein30gluconolactonase AT akihitoishigami structuralbasisoftheglactoneringformationinascorbicacidbiosynthesisbythesenescencemarkerprotein30gluconolactonase AT toshiyasenda structuralbasisoftheglactoneringformationinascorbicacidbiosynthesisbythesenescencemarkerprotein30gluconolactonase
_version_	1718422685883564032

Structural basis of the γ-lactone-ring formation in ascorbic acid biosynthesis by the senescence marker protein-30/gluconolactonase.

Ejemplares similares