1coz
From Proteopedia
(New page: 200px<br /><applet load="1coz" size="450" color="white" frame="true" align="right" spinBox="true" caption="1coz, resolution 2.00Å" /> '''CTP:GLYCEROL-3-PHOSP...) |
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| - | [[Image:1coz.gif|left|200px]]<br /><applet load="1coz" size=" | + | [[Image:1coz.gif|left|200px]]<br /><applet load="1coz" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1coz, resolution 2.00Å" /> | caption="1coz, resolution 2.00Å" /> | ||
'''CTP:GLYCEROL-3-PHOSPHATE CYTIDYLYLTRANSFERASE FROM BACILLUS SUBTILIS'''<br /> | '''CTP:GLYCEROL-3-PHOSPHATE CYTIDYLYLTRANSFERASE FROM BACILLUS SUBTILIS'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: The formation of critical intermediates in the biosynthesis of | + | BACKGROUND: The formation of critical intermediates in the biosynthesis of lipids and complex carbohydrates is carried out by cytidylyltransferases, which utilize CTP to form activated CDP-alcohols or CMP-acid sugars plus inorganic pyrophosphate. Several cytidylyltransferases are related and constitute a conserved family of enzymes. The eukaryotic members of the family are complex enzymes with multiple regulatory regions or repeated catalytic domains, whereas the bacterial enzyme, CTP:glycerol-3-phosphate cytidylyltransferase (GCT), contains only the catalytic domain. Thus, GCT provides an excellent model for the study of catalysis by the eukaryotic cytidylyltransferases. RESULTS: The crystal structure of GCT from Bacillus subtilis has been determined by multiwavelength anomalous diffraction using a mercury derivative and refined to 2.0 A resolution (R(factor) 0.196; R(free) 0.255). GCT is a homodimer; each monomer comprises an alpha/beta fold with a central 3-2-1-4-5 parallel beta sheet. Additional helices and loops extending from the alpha/beta core form a bowl that binds substrates. CTP, bound at each active site of the homodimer, interacts with the conserved (14)HXGH and (113)RTXGISTT motifs. The dimer interface incorporates part of a third motif, (63)RYVDEVI, and includes hydrophobic residues adjoining the HXGH sequence. CONCLUSIONS: Structure superpositions relate GCT to the catalytic domains from class I aminoacyl-tRNA synthetases, and thus expand the tRNA synthetase family of folds to include the catalytic domains of the family of cytidylyltransferases. GCT and aminoacyl-tRNA synthetases catalyze analogous reactions, bind nucleotides in similar U-shaped conformations, and depend on histidines from analogous HXGH motifs for activity. The structural and other similarities support proposals that GCT, like the synthetases, catalyzes nucleotidyl transfer by stabilizing a pentavalent transition state at the alpha-phosphate of CTP. |
==About this Structure== | ==About this Structure== | ||
| - | 1COZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bacillus_subtilis Bacillus subtilis] with CTP as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Glycerol-3-phosphate_cytidylyltransferase Glycerol-3-phosphate cytidylyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.39 2.7.7.39] Full crystallographic information is available from [http:// | + | 1COZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bacillus_subtilis Bacillus subtilis] with <scene name='pdbligand=CTP:'>CTP</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Glycerol-3-phosphate_cytidylyltransferase Glycerol-3-phosphate cytidylyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.39 2.7.7.39] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1COZ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Kent, C.]] | [[Category: Kent, C.]] | ||
| - | [[Category: Ludwig, M | + | [[Category: Ludwig, M L.]] |
| - | [[Category: Park, Y | + | [[Category: Park, Y S.]] |
[[Category: Sanker, S.]] | [[Category: Sanker, S.]] | ||
| - | [[Category: Weber, C | + | [[Category: Weber, C H.]] |
[[Category: CTP]] | [[Category: CTP]] | ||
[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:08:13 2008'' |
Revision as of 10:08, 21 February 2008
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CTP:GLYCEROL-3-PHOSPHATE CYTIDYLYLTRANSFERASE FROM BACILLUS SUBTILIS
Overview
BACKGROUND: The formation of critical intermediates in the biosynthesis of lipids and complex carbohydrates is carried out by cytidylyltransferases, which utilize CTP to form activated CDP-alcohols or CMP-acid sugars plus inorganic pyrophosphate. Several cytidylyltransferases are related and constitute a conserved family of enzymes. The eukaryotic members of the family are complex enzymes with multiple regulatory regions or repeated catalytic domains, whereas the bacterial enzyme, CTP:glycerol-3-phosphate cytidylyltransferase (GCT), contains only the catalytic domain. Thus, GCT provides an excellent model for the study of catalysis by the eukaryotic cytidylyltransferases. RESULTS: The crystal structure of GCT from Bacillus subtilis has been determined by multiwavelength anomalous diffraction using a mercury derivative and refined to 2.0 A resolution (R(factor) 0.196; R(free) 0.255). GCT is a homodimer; each monomer comprises an alpha/beta fold with a central 3-2-1-4-5 parallel beta sheet. Additional helices and loops extending from the alpha/beta core form a bowl that binds substrates. CTP, bound at each active site of the homodimer, interacts with the conserved (14)HXGH and (113)RTXGISTT motifs. The dimer interface incorporates part of a third motif, (63)RYVDEVI, and includes hydrophobic residues adjoining the HXGH sequence. CONCLUSIONS: Structure superpositions relate GCT to the catalytic domains from class I aminoacyl-tRNA synthetases, and thus expand the tRNA synthetase family of folds to include the catalytic domains of the family of cytidylyltransferases. GCT and aminoacyl-tRNA synthetases catalyze analogous reactions, bind nucleotides in similar U-shaped conformations, and depend on histidines from analogous HXGH motifs for activity. The structural and other similarities support proposals that GCT, like the synthetases, catalyzes nucleotidyl transfer by stabilizing a pentavalent transition state at the alpha-phosphate of CTP.
About this Structure
1COZ is a Single protein structure of sequence from Bacillus subtilis with as ligand. Active as Glycerol-3-phosphate cytidylyltransferase, with EC number 2.7.7.39 Full crystallographic information is available from OCA.
Reference
A prototypical cytidylyltransferase: CTP:glycerol-3-phosphate cytidylyltransferase from bacillus subtilis., Weber CH, Park YS, Sanker S, Kent C, Ludwig ML, Structure. 1999 Sep 15;7(9):1113-24. PMID:10508782
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