1q4g
From Proteopedia
(New page: 200px<br /><applet load="1q4g" size="450" color="white" frame="true" align="right" spinBox="true" caption="1q4g, resolution 2.00Å" /> '''2.0 Angstrom Crystal...) |
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| - | [[Image:1q4g.jpg|left|200px]]<br /><applet load="1q4g" size=" | + | [[Image:1q4g.jpg|left|200px]]<br /><applet load="1q4g" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1q4g, resolution 2.00Å" /> | caption="1q4g, resolution 2.00Å" /> | ||
'''2.0 Angstrom Crystal Structure of Ovine Prostaglandin H2 Synthase-1, in complex with alpha-methyl-4-biphenylacetic acid'''<br /> | '''2.0 Angstrom Crystal Structure of Ovine Prostaglandin H2 Synthase-1, in complex with alpha-methyl-4-biphenylacetic acid'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Prostaglandin H2 synthase (EC 1.14.99.1) is an integral membrane enzyme | + | Prostaglandin H2 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 A resolution X-ray crystal structure of ovine prostaglandin H2 synthase-1 in complex with alpha-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. |
==About this Structure== | ==About this Structure== | ||
| - | 1Q4G is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Ovis_aries Ovis aries] with BOG, BFL, HEM and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Prostaglandin-endoperoxide_synthase Prostaglandin-endoperoxide synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.99.1 1.14.99.1] Full crystallographic information is available from [http:// | + | 1Q4G is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Ovis_aries Ovis aries] with <scene name='pdbligand=BOG:'>BOG</scene>, <scene name='pdbligand=BFL:'>BFL</scene>, <scene name='pdbligand=HEM:'>HEM</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Prostaglandin-endoperoxide_synthase Prostaglandin-endoperoxide synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.99.1 1.14.99.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q4G OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Gupta, K.]] | [[Category: Gupta, K.]] | ||
| - | [[Category: Katz, A | + | [[Category: Katz, A K.]] |
| - | [[Category: Kaub, C | + | [[Category: Kaub, C J.]] |
| - | [[Category: Loll, P | + | [[Category: Loll, P J.]] |
| - | [[Category: Selinksy, B | + | [[Category: Selinksy, B S.]] |
[[Category: BFL]] | [[Category: BFL]] | ||
[[Category: BOG]] | [[Category: BOG]] | ||
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[[Category: prostaglandin synthase]] | [[Category: prostaglandin synthase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:35:46 2008'' |
Revision as of 12:35, 21 February 2008
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2.0 Angstrom Crystal Structure of Ovine Prostaglandin H2 Synthase-1, in complex with alpha-methyl-4-biphenylacetic acid
Overview
Prostaglandin H2 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 A resolution X-ray crystal structure of ovine prostaglandin H2 synthase-1 in complex with alpha-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.
About this Structure
1Q4G is a Single protein structure of sequence from Ovis aries with , , and as ligands. Active as Prostaglandin-endoperoxide synthase, with EC number 1.14.99.1 Full crystallographic information is available from OCA.
Reference
The 2.0 A resolution crystal structure of prostaglandin H2 synthase-1: structural insights into an unusual peroxidase., Gupta K, Selinsky BS, Kaub CJ, Katz AK, Loll PJ, J Mol Biol. 2004 Jan 9;335(2):503-18. PMID:14672659
Page seeded by OCA on Thu Feb 21 14:35:46 2008
Categories: Ovis aries | Prostaglandin-endoperoxide synthase | Single protein | Gupta, K. | Katz, A K. | Kaub, C J. | Loll, P J. | Selinksy, B S. | BFL | BOG | GOL | HEM | Cyclooxygenase | Egf-like domain | Membrane binding domain | Non-steroidal anti-inflammatory drug | Peroxidase | Prostaglandin synthase
