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Crystal structure of a divalent metal ion transporter CorA at 2.9 angstrom resolution
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. (Pär Nordlund)
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
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2006 (English)In: Science, ISSN 0036-8075, Vol. 313, no 5785, 354-357 p.Article in journal (Refereed) Published
Abstract [en]

CorA family members are ubiquitously distributed transporters of divalent metal cations and are considered to be the primary Mg2 transporter of Bacteria and Archaea. We have determined a 2.9 angstrom resolution structure of CorA from Thermotoga maritima that reveals a pentameric cone– shaped protein. Two potential regulatory metal binding sites are found in the N-terminal domain that bind both Mg2+ and Co2+. The structure of CorA supports an efflux system involving dehydration and rehydration of divalent metal ions potentially mediated by a ring of conserved aspartate residues at the cytoplasmic entrance and a carbonyl funnel at the periplasmic side of the pore.

Place, publisher, year, edition, pages
2006. Vol. 313, no 5785, 354-357 p.
Keyword [en]
Magnesium, cora, transporter, channel, membrane proteins
National Category
Biochemistry and Molecular Biology
Research subject
Structural Biology
URN: urn:nbn:se:su:diva-29989DOI: 10.1126/science.1127121OAI: diva2:241101
Available from: 2009-10-01 Created: 2009-09-27 Last updated: 2009-10-01Bibliographically approved
In thesis
1. Structural biology of integral membrane proteins - From methods to molecular mechanisms
Open this publication in new window or tab >>Structural biology of integral membrane proteins - From methods to molecular mechanisms
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Membrane proteins are vital components in the cell and crucial for the proliferation of all living organisms. Unfortunately our collective knowledge of structures of membrane proteins is very limited, as compared to the information available on soluble proteins. This is to a large extent due to the outstanding challenge of working with membrane proteins and the relatively high cost associated with determining a membrane protein structure.  Therefore, the establishment of efficient methods and means for the production and crystallization of membrane proteins is urgently needed. The two methods explored in this thesis  are aimed to achieve rapid optimization of expression and purification conditions of membrane proteins, thereby allowing for the rapid production of more suitable samples for crystallization trials.

Despite the challenges in membrane protein structure determination two structures are presented in the thesis:

The first structure determined is of the CorA magnesium transporter from Thermotoga maritima will be the focus of this thesis. The CorA revealed a pentameric protein in a closed state. The presence of two regulatory metal binding sites is suggested, as well as a putative magnesium ion bound in the ion conductive pathway.

The second structure is of the human enzyme LTC4-synthase, which catalyzes the pivotal step in eicosanoid synthesis by the conjugation of glutathione to LTA4, a reactive epoxide-containing derivative from arachidonic acid. The products of this step, the so-called cysteinyl leukotrienes are potent inflammatory mediators making this enzyme a potential drug target. The structure reveals a charged binding pocket for a horseshoe-shaped glutathione, and a hydrophobic binding pocket for a lipophilic LTA4 molecule. Based on the structure a key residue for catalysis has been identified, Arg 104, which is proposed to play a critical role in activating the thiol group of glutathione for the nucleophilic attack on LTA4.

Place, publisher, year, edition, pages
Stockholm: Department of Biochemistry and Biophysics, Stockholm Univeristy, 2009. 59 p.
membrane proteins, CorA, magnesium transport, screening, Leukotriene C4 synthase, detergents
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
urn:nbn:se:su:diva-30069 (URN)978-91-628-7899-3 (ISBN)
Public defence
2009-10-29, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 14:00 (English)
Available from: 2009-10-07 Created: 2009-10-01 Last updated: 2012-08-10Bibliographically approved

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