The X-ray crystal structure of Escherichia coli succinic semialdehyde dehydrogenase; structural insights into NADP+/enzyme interactions.

<h4>Background</h4>In mammals succinic semialdehyde dehydrogenase (SSADH) plays an essential role in the metabolism of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) to succinic acid (SA). Deficiency of SSADH in humans results in elevated levels of GABA and gamma-Hydroxyb...

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Autores principales:	Christopher G Langendorf, Trevor L G Key, Gustavo Fenalti, Wan-Ting Kan, Ashley M Buckle, Tom Caradoc-Davies, Kellie L Tuck, Ruby H P Law, James C Whisstock
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a516366723734c67a8727a844c5aaebb
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spelling	oai:doaj.org-article:a516366723734c67a8727a844c5aaebb2021-11-25T06:25:43ZThe X-ray crystal structure of Escherichia coli succinic semialdehyde dehydrogenase; structural insights into NADP+/enzyme interactions.1932-620310.1371/journal.pone.0009280https://doaj.org/article/a516366723734c67a8727a844c5aaebb2010-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20174634/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>In mammals succinic semialdehyde dehydrogenase (SSADH) plays an essential role in the metabolism of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) to succinic acid (SA). Deficiency of SSADH in humans results in elevated levels of GABA and gamma-Hydroxybutyric acid (GHB), which leads to psychomotor retardation, muscular hypotonia, non-progressive ataxia and seizures. In Escherichia coli, two genetically distinct forms of SSADHs had been described that are essential for preventing accumulation of toxic levels of succinic semialdehyde (SSA) in cells.<h4>Methodology/principal findings</h4>Here we structurally characterise SSADH encoded by the E coli gabD gene by X-ray crystallographic studies and compare these data with the structure of human SSADH. In the E. coli SSADH structure, electron density for the complete NADP+ cofactor in the binding sites is clearly evident; these data in particular revealing how the nicotinamide ring of the cofactor is positioned in each active site.<h4>Conclusions/significance</h4>Our structural data suggest that a deletion of three amino acids in E. coli SSADH permits this enzyme to use NADP+, whereas in contrast the human enzyme utilises NAD+. Furthermore, the structure of E. coli SSADH gives additional insight into human mutations that result in disease.Christopher G LangendorfTrevor L G KeyGustavo FenaltiWan-Ting KanAshley M BuckleTom Caradoc-DaviesKellie L TuckRuby H P LawJames C WhisstockPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 2, p e9280 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Christopher G Langendorf Trevor L G Key Gustavo Fenalti Wan-Ting Kan Ashley M Buckle Tom Caradoc-Davies Kellie L Tuck Ruby H P Law James C Whisstock The X-ray crystal structure of Escherichia coli succinic semialdehyde dehydrogenase; structural insights into NADP+/enzyme interactions.
description	<h4>Background</h4>In mammals succinic semialdehyde dehydrogenase (SSADH) plays an essential role in the metabolism of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) to succinic acid (SA). Deficiency of SSADH in humans results in elevated levels of GABA and gamma-Hydroxybutyric acid (GHB), which leads to psychomotor retardation, muscular hypotonia, non-progressive ataxia and seizures. In Escherichia coli, two genetically distinct forms of SSADHs had been described that are essential for preventing accumulation of toxic levels of succinic semialdehyde (SSA) in cells.<h4>Methodology/principal findings</h4>Here we structurally characterise SSADH encoded by the E coli gabD gene by X-ray crystallographic studies and compare these data with the structure of human SSADH. In the E. coli SSADH structure, electron density for the complete NADP+ cofactor in the binding sites is clearly evident; these data in particular revealing how the nicotinamide ring of the cofactor is positioned in each active site.<h4>Conclusions/significance</h4>Our structural data suggest that a deletion of three amino acids in E. coli SSADH permits this enzyme to use NADP+, whereas in contrast the human enzyme utilises NAD+. Furthermore, the structure of E. coli SSADH gives additional insight into human mutations that result in disease.
format	article
author	Christopher G Langendorf Trevor L G Key Gustavo Fenalti Wan-Ting Kan Ashley M Buckle Tom Caradoc-Davies Kellie L Tuck Ruby H P Law James C Whisstock
author_facet	Christopher G Langendorf Trevor L G Key Gustavo Fenalti Wan-Ting Kan Ashley M Buckle Tom Caradoc-Davies Kellie L Tuck Ruby H P Law James C Whisstock
author_sort	Christopher G Langendorf
title	The X-ray crystal structure of Escherichia coli succinic semialdehyde dehydrogenase; structural insights into NADP+/enzyme interactions.
title_short	The X-ray crystal structure of Escherichia coli succinic semialdehyde dehydrogenase; structural insights into NADP+/enzyme interactions.
title_full	The X-ray crystal structure of Escherichia coli succinic semialdehyde dehydrogenase; structural insights into NADP+/enzyme interactions.
title_fullStr	The X-ray crystal structure of Escherichia coli succinic semialdehyde dehydrogenase; structural insights into NADP+/enzyme interactions.
title_full_unstemmed	The X-ray crystal structure of Escherichia coli succinic semialdehyde dehydrogenase; structural insights into NADP+/enzyme interactions.
title_sort	x-ray crystal structure of escherichia coli succinic semialdehyde dehydrogenase; structural insights into nadp+/enzyme interactions.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/a516366723734c67a8727a844c5aaebb
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The X-ray crystal structure of Escherichia coli succinic semialdehyde dehydrogenase; structural insights into NADP+/enzyme interactions.

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