1qd1
From Proteopedia
(New page: 200px<br /><applet load="1qd1" size="450" color="white" frame="true" align="right" spinBox="true" caption="1qd1, resolution 1.7Å" /> '''THE CRYSTAL STRUCTURE...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1qd1.jpg|left|200px]]<br /><applet load="1qd1" size=" | + | [[Image:1qd1.jpg|left|200px]]<br /><applet load="1qd1" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1qd1, resolution 1.7Å" /> | caption="1qd1, resolution 1.7Å" /> | ||
'''THE CRYSTAL STRUCTURE OF THE FORMIMINOTRANSFERASE DOMAIN OF FORMIMINOTRANSFERASE-CYCLODEAMINASE.'''<br /> | '''THE CRYSTAL STRUCTURE OF THE FORMIMINOTRANSFERASE DOMAIN OF FORMIMINOTRANSFERASE-CYCLODEAMINASE.'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: The bifunctional enzyme formiminotransferase-cyclodeaminase | + | BACKGROUND: The bifunctional enzyme formiminotransferase-cyclodeaminase (FTCD) contains two active sites at different positions on the protein structure. The enzyme binds a gamma-linked polyglutamylated form of the tetrahydrofolate substrate and channels the product of the transferase reaction from the transferase active site to the cyclodeaminase active site. Structural studies of this bifunctional enzyme and its monofunctional domains will provide insight into the mechanism of substrate channeling and the two catalytic reactions. RESULTS: The crystal structure of the formiminotransferase (FT) domain of FTCD has been determined in the presence of a product analog, folinic acid. The overall structure shows that the FT domain comprises two subdomains that adopt a novel alpha/beta fold. Inspection of the folinic acid binding site reveals an electrostatic tunnel traversing the width of the molecule. The distribution of charged residues in the tunnel provides insight into the possible mode of substrate binding and channeling. The electron density reveals that the non-natural stereoisomer, (6R)-folinic acid, binds to the protein; this observation suggests a mechanism for product release. In addition, a single molecule of glycerol is bound to the enzyme and indicates a putative binding site for formiminoglutamate. CONCLUSIONS: The structure of the FT domain in the presence of folinic acid reveals a possible novel mechanism for substrate channeling. The position of the folinic acid and a bound glycerol molecule near to the sidechain of His82 suggests that this residue may act as the catalytic base required for the formiminotransferase mechanism. |
==About this Structure== | ==About this Structure== | ||
| - | 1QD1 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with FON and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Glutamate_formimidoyltransferase Glutamate formimidoyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.2.5 2.1.2.5] Full crystallographic information is available from [http:// | + | 1QD1 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with <scene name='pdbligand=FON:'>FON</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Glutamate_formimidoyltransferase Glutamate formimidoyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.2.5 2.1.2.5] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QD1 OCA]. |
==Reference== | ==Reference== | ||
| Line 15: | Line 15: | ||
[[Category: Sus scrofa]] | [[Category: Sus scrofa]] | ||
[[Category: Kohls, D.]] | [[Category: Kohls, D.]] | ||
| - | [[Category: MacKenzie, R | + | [[Category: MacKenzie, R E.]] |
[[Category: Purisima, E.]] | [[Category: Purisima, E.]] | ||
[[Category: Sulea, T.]] | [[Category: Sulea, T.]] | ||
| Line 25: | Line 25: | ||
[[Category: functional dimer]] | [[Category: functional dimer]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:38:23 2008'' |
Revision as of 12:38, 21 February 2008
|
THE CRYSTAL STRUCTURE OF THE FORMIMINOTRANSFERASE DOMAIN OF FORMIMINOTRANSFERASE-CYCLODEAMINASE.
Overview
BACKGROUND: The bifunctional enzyme formiminotransferase-cyclodeaminase (FTCD) contains two active sites at different positions on the protein structure. The enzyme binds a gamma-linked polyglutamylated form of the tetrahydrofolate substrate and channels the product of the transferase reaction from the transferase active site to the cyclodeaminase active site. Structural studies of this bifunctional enzyme and its monofunctional domains will provide insight into the mechanism of substrate channeling and the two catalytic reactions. RESULTS: The crystal structure of the formiminotransferase (FT) domain of FTCD has been determined in the presence of a product analog, folinic acid. The overall structure shows that the FT domain comprises two subdomains that adopt a novel alpha/beta fold. Inspection of the folinic acid binding site reveals an electrostatic tunnel traversing the width of the molecule. The distribution of charged residues in the tunnel provides insight into the possible mode of substrate binding and channeling. The electron density reveals that the non-natural stereoisomer, (6R)-folinic acid, binds to the protein; this observation suggests a mechanism for product release. In addition, a single molecule of glycerol is bound to the enzyme and indicates a putative binding site for formiminoglutamate. CONCLUSIONS: The structure of the FT domain in the presence of folinic acid reveals a possible novel mechanism for substrate channeling. The position of the folinic acid and a bound glycerol molecule near to the sidechain of His82 suggests that this residue may act as the catalytic base required for the formiminotransferase mechanism.
About this Structure
1QD1 is a Single protein structure of sequence from Sus scrofa with and as ligands. Active as Glutamate formimidoyltransferase, with EC number 2.1.2.5 Full crystallographic information is available from OCA.
Reference
The crystal structure of the formiminotransferase domain of formiminotransferase-cyclodeaminase: implications for substrate channeling in a bifunctional enzyme., Kohls D, Sulea T, Purisima EO, MacKenzie RE, Vrielink A, Structure. 2000 Jan 15;8(1):35-46. PMID:10673422
Page seeded by OCA on Thu Feb 21 14:38:23 2008
