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Crystal structure of HutZ, a heme storage protein from Vibrio cholerae: A structural mismatch observed in the region of high sequence conservation

BACKGROUND: HutZ is the sole heme storage protein identified in the pathogenic bacterium Vibrio cholerae and is required for optimal heme utilization. However, no heme oxygenase activity has been observed with this protein. Thus far, HutZ’s structure and heme-binding mechanism are unknown. RESULTS:...

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Autores principales: Liu, Xiuhua, Gong, Jing, Wei, Tiandi, Wang, Zhi, Du, Qian, Zhu, Deyu, Huang, Yan, Xu, Sujuan, Gu, Lichuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3472187/
https://www.ncbi.nlm.nih.gov/pubmed/23013214
http://dx.doi.org/10.1186/1472-6807-12-23
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author Liu, Xiuhua
Gong, Jing
Wei, Tiandi
Wang, Zhi
Du, Qian
Zhu, Deyu
Huang, Yan
Xu, Sujuan
Gu, Lichuan
author_facet Liu, Xiuhua
Gong, Jing
Wei, Tiandi
Wang, Zhi
Du, Qian
Zhu, Deyu
Huang, Yan
Xu, Sujuan
Gu, Lichuan
author_sort Liu, Xiuhua
collection PubMed
description BACKGROUND: HutZ is the sole heme storage protein identified in the pathogenic bacterium Vibrio cholerae and is required for optimal heme utilization. However, no heme oxygenase activity has been observed with this protein. Thus far, HutZ’s structure and heme-binding mechanism are unknown. RESULTS: We report the first crystal structure of HutZ in a homodimer determined at 2.0 Å resolution. The HutZ structure adopted a typical split-barrel fold. Through a docking study and site-directed mutagenesis, a heme-binding model for the HutZ dimer is proposed. Very interestingly, structural superimposition of HutZ and its homologous protein HugZ, a heme oxygenase from Helicobacter pylori, exhibited a structural mismatch of one amino acid residue in β6 of HutZ, although residues involved in this region are highly conserved in both proteins. Derived homologous models of different single point variants with model evaluations suggested that Pro(140) of HutZ, corresponding to Phe(215) of HugZ, might have been the main contributor to the structural mismatch. This mismatch initiates more divergent structural characteristics towards their C-terminal regions, which are essential features for the heme-binding of HugZ as a heme oxygenase. CONCLUSIONS: HutZ’s deficiency in heme oxygenase activity might derive from its residue shift relative to the heme oxygenase HugZ. This residue shift also emphasized a limitation of the traditional template selection criterion for homology modeling.
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spelling pubmed-34721872012-10-17 Crystal structure of HutZ, a heme storage protein from Vibrio cholerae: A structural mismatch observed in the region of high sequence conservation Liu, Xiuhua Gong, Jing Wei, Tiandi Wang, Zhi Du, Qian Zhu, Deyu Huang, Yan Xu, Sujuan Gu, Lichuan BMC Struct Biol Research Article BACKGROUND: HutZ is the sole heme storage protein identified in the pathogenic bacterium Vibrio cholerae and is required for optimal heme utilization. However, no heme oxygenase activity has been observed with this protein. Thus far, HutZ’s structure and heme-binding mechanism are unknown. RESULTS: We report the first crystal structure of HutZ in a homodimer determined at 2.0 Å resolution. The HutZ structure adopted a typical split-barrel fold. Through a docking study and site-directed mutagenesis, a heme-binding model for the HutZ dimer is proposed. Very interestingly, structural superimposition of HutZ and its homologous protein HugZ, a heme oxygenase from Helicobacter pylori, exhibited a structural mismatch of one amino acid residue in β6 of HutZ, although residues involved in this region are highly conserved in both proteins. Derived homologous models of different single point variants with model evaluations suggested that Pro(140) of HutZ, corresponding to Phe(215) of HugZ, might have been the main contributor to the structural mismatch. This mismatch initiates more divergent structural characteristics towards their C-terminal regions, which are essential features for the heme-binding of HugZ as a heme oxygenase. CONCLUSIONS: HutZ’s deficiency in heme oxygenase activity might derive from its residue shift relative to the heme oxygenase HugZ. This residue shift also emphasized a limitation of the traditional template selection criterion for homology modeling. BioMed Central 2012-09-26 /pmc/articles/PMC3472187/ /pubmed/23013214 http://dx.doi.org/10.1186/1472-6807-12-23 Text en Copyright ©2012 Liu et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Liu, Xiuhua
Gong, Jing
Wei, Tiandi
Wang, Zhi
Du, Qian
Zhu, Deyu
Huang, Yan
Xu, Sujuan
Gu, Lichuan
Crystal structure of HutZ, a heme storage protein from Vibrio cholerae: A structural mismatch observed in the region of high sequence conservation
title Crystal structure of HutZ, a heme storage protein from Vibrio cholerae: A structural mismatch observed in the region of high sequence conservation
title_full Crystal structure of HutZ, a heme storage protein from Vibrio cholerae: A structural mismatch observed in the region of high sequence conservation
title_fullStr Crystal structure of HutZ, a heme storage protein from Vibrio cholerae: A structural mismatch observed in the region of high sequence conservation
title_full_unstemmed Crystal structure of HutZ, a heme storage protein from Vibrio cholerae: A structural mismatch observed in the region of high sequence conservation
title_short Crystal structure of HutZ, a heme storage protein from Vibrio cholerae: A structural mismatch observed in the region of high sequence conservation
title_sort crystal structure of hutz, a heme storage protein from vibrio cholerae: a structural mismatch observed in the region of high sequence conservation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3472187/
https://www.ncbi.nlm.nih.gov/pubmed/23013214
http://dx.doi.org/10.1186/1472-6807-12-23
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