Journal article
The 2.0 Å Resolution Crystal Structure of Prostaglandin H 2 Synthase-1: Structural Insights into an Unusual Peroxidase
Journal of molecular biology, v 335(2), pp 503-518
2004
PMID: 14672659
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Prostaglandin H
2 synthase (EC 1.14.99.1) is an integral membrane enzyme containing a cyclooxygenase site, which is the target for the non-steroidal anti-inflammatory drugs, and a spatially distinct peroxidase site. Previous crystallographic studies of this clinically important drug target have been hindered by low resolution. We present here the 2.0
Å resolution X-ray crystal structure of ovine prostaglandin H
2 synthase-1 in complex with α-methyl-4-biphenylacetic acid, a defluorinated analog of the non-steroidal anti-inflammatory drug flurbiprofen. Detergent molecules are seen to bind to the protein's membrane-binding domain, and their positions suggest the depth to which this domain is likely to penetrate into the lipid bilayer. The relation of the enzyme's proximal heme ligand His388 to the heme iron is atypical for a peroxidase; the iron–histidine bond is unusually long and a substantial tilt angle is observed between the heme and imidazole planes. A molecule of glycerol, used as a cryoprotectant during diffraction experiments, is seen to bind in the peroxidase site, offering the first view of any ligand in this active site. Insights gained from glycerol binding may prove useful in the design of a peroxidase-specific ligand.
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Details
- Title
- The 2.0 Å Resolution Crystal Structure of Prostaglandin H 2 Synthase-1: Structural Insights into an Unusual Peroxidase
- Creators
- Kushol Gupta - Department of Biochemistry, Drexel University College of Medicine, 245 N 15th Street, Mailstop 497, Philadelphia, PA 19102-1192, USABarry S Selinsky - Department of Chemistry, Villanova University, Villanova, PA 19085, USACarl J Kaub - Department of Chemistry, Villanova University, Villanova, PA 19085, USAAmy K Katz - Department of Biochemistry, Drexel University College of Medicine, 245 N 15th Street, Mailstop 497, Philadelphia, PA 19102-1192, USAPatrick J Loll - Department of Biochemistry, Drexel University College of Medicine, 245 N 15th Street, Mailstop 497, Philadelphia, PA 19102-1192, USA
- Publication Details
- Journal of molecular biology, v 335(2), pp 503-518
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000188164000011
- Scopus ID
- 2-s2.0-0345735668
- Other Identifier
- 991014878507804721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology