1ae1
From Proteopedia
(New page: 200px<br /><applet load="1ae1" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ae1, resolution 2.40Å" /> '''TROPINONE REDUCTASE-...) |
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| - | [[Image:1ae1.gif|left|200px]]<br /><applet load="1ae1" size=" | + | [[Image:1ae1.gif|left|200px]]<br /><applet load="1ae1" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1ae1, resolution 2.40Å" /> | caption="1ae1, resolution 2.40Å" /> | ||
'''TROPINONE REDUCTASE-I COMPLEX WITH NADP'''<br /> | '''TROPINONE REDUCTASE-I COMPLEX WITH NADP'''<br /> | ||
==Overview== | ==Overview== | ||
| - | A pair of tropinone reductases (TRs) share 64% of the same amino acid | + | A pair of tropinone reductases (TRs) share 64% of the same amino acid residues and belong to the short-chain dehydrogenase/reductase family. In the synthesis of tropane alkaloids in several medicinal plants, the TRs reduce a carbonyl group of an alkaloid intermediate, tropinone, to hydroxy groups with different diastereomeric configurations. To clarify the structural basis for their different reaction stereospecificities, we determined the crystal structures of the two enzymes at 2.4- and 2.3-A resolutions. The overall folding of the two enzymes was almost identical. The conservation was not confined within the core domains that are conserved within the protein family but extended outside the core domain where each family member has its characteristic structure. The binding sites for the cofactor and the positions of the active site residues were well conserved between the two TRs. The substrate binding site was composed mostly of hydrophobic amino acids in both TRs, but the presence of different charged residues conferred different electrostatic environments on the two enzymes. A modeling study indicated that these charged residues play a major role in controlling the binding orientation of tropinone within the substrate binding site, thereby determining the stereospecificity of the reaction product. The results obtained herein raise the possibility that in certain cases different stereospecificities can be acquired in enzymes by changing a few amino acid residues within substrate binding sites. |
==About this Structure== | ==About this Structure== | ||
| - | 1AE1 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Datura_stramonium Datura stramonium] with NAP as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Tropinone_reductase_II Tropinone reductase II], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.236 1.1.1.236] Full crystallographic information is available from [http:// | + | 1AE1 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Datura_stramonium Datura stramonium] with <scene name='pdbligand=NAP:'>NAP</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Tropinone_reductase_II Tropinone reductase II], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.236 1.1.1.236] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AE1 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: tropane alkaloid biosynthesis]] | [[Category: tropane alkaloid biosynthesis]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:43:34 2008'' |
Revision as of 09:43, 21 February 2008
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TROPINONE REDUCTASE-I COMPLEX WITH NADP
Overview
A pair of tropinone reductases (TRs) share 64% of the same amino acid residues and belong to the short-chain dehydrogenase/reductase family. In the synthesis of tropane alkaloids in several medicinal plants, the TRs reduce a carbonyl group of an alkaloid intermediate, tropinone, to hydroxy groups with different diastereomeric configurations. To clarify the structural basis for their different reaction stereospecificities, we determined the crystal structures of the two enzymes at 2.4- and 2.3-A resolutions. The overall folding of the two enzymes was almost identical. The conservation was not confined within the core domains that are conserved within the protein family but extended outside the core domain where each family member has its characteristic structure. The binding sites for the cofactor and the positions of the active site residues were well conserved between the two TRs. The substrate binding site was composed mostly of hydrophobic amino acids in both TRs, but the presence of different charged residues conferred different electrostatic environments on the two enzymes. A modeling study indicated that these charged residues play a major role in controlling the binding orientation of tropinone within the substrate binding site, thereby determining the stereospecificity of the reaction product. The results obtained herein raise the possibility that in certain cases different stereospecificities can be acquired in enzymes by changing a few amino acid residues within substrate binding sites.
About this Structure
1AE1 is a Single protein structure of sequence from Datura stramonium with as ligand. Active as Tropinone reductase II, with EC number 1.1.1.236 Full crystallographic information is available from OCA.
Reference
Crystal structures of two tropinone reductases: different reaction stereospecificities in the same protein fold., Nakajima K, Yamashita A, Akama H, Nakatsu T, Kato H, Hashimoto T, Oda J, Yamada Y, Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):4876-81. PMID:9560196
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