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Open Access 01-06-2011 | Original Article

Structural basis of fumarate hydratase deficiency

Authors: Sarah Picaud, Kathryn L. Kavanagh, Wyatt W. Yue, Wen Hwa Lee, Susanne Muller-Knapp, Opher Gileadi, James Sacchettini, Udo Oppermann

Published in: Journal of Inherited Metabolic Disease | Issue 3/2011

Abstract

Fumarate hydratase catalyzes the stereospecific hydration across the olefinic double bond in fumarate leading to L-malate. The enzyme is expressed in mitochondrial and cytosolic compartments, and participates in the Krebs cycle in mitochondria, as well as in regulation of cytosolic fumarate levels. Fumarate hydratase deficiency is an autosomal recessive trait presenting as metabolic disorder with severe encephalopathy, seizures and poor neurological outcome. Heterozygous mutations are associated with a predisposition to cutaneous and uterine leiomyomas and to renal cancer. The crystal structure of human fumarate hydratase shows that mutations can be grouped into two distinct classes either affecting structural integrity of the core enzyme architecture, or are localized around the enzyme active site.

An interactive version of this manuscript (which may contain additional mutations appended after acceptance of this manuscript) may be found on the SSIEM website at:http://www.ssiem.org/resources/structures/FH.

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Title: Structural basis of fumarate hydratase deficiency
Authors: Sarah Picaud
Kathryn L. Kavanagh
Wyatt W. Yue
Wen Hwa Lee
Susanne Muller-Knapp
Opher Gileadi
James Sacchettini
Udo Oppermann
Publication date: 01-06-2011
Publisher: Springer Netherlands
Published in: Journal of Inherited Metabolic Disease / Issue 3/2011
Print ISSN: 0141-8955
Electronic ISSN: 1573-2665
DOI: https://doi.org/10.1007/s10545-011-9294-8

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