2iyo: Difference between revisions

Line 4:

==Overview==

Crystal structures of recombinant Lactococcus lactis 6-phosphogluconate, dehydrogenase (LlPDH) in complex with substrate, cofactor, product and, inhibitors have been determined. LlPDH shares significant sequence, identity with the enzymes from sheep liver and the protozoan parasite, Trypanosoma brucei for which structures have been reported. Comparisons, indicate that the key residues in the active site are highly conserved, as, are the interactions with the cofactor and the product ribulose, 5-phosphate. However, there are differences in the conformation of the, substrate 6-phosphogluconate which may reflect distinct states relevant to, catalysis. Analysis of the complex formed with the potent inhibitor, 4-phospho-d-erythronohydroxamic acid, suggests that this molecule does, indeed mimic the high-energy intermediate state that it was designed to., The analysis also identified, as a contaminant by-product of the inhibitor, synthesis, 4-phospho-d-erythronamide, which binds in similar fashion., LlPDH can now serve as a model system for structure-based inhibitor design, targeting the enzyme from Trypanosoma species.

Crystal structures of recombinant Lactococcus lactis 6-phosphogluconate dehydrogenase (LlPDH) in complex with substrate, cofactor, product and inhibitors have been determined. LlPDH shares significant sequence identity with the enzymes from sheep liver and the protozoan parasite Trypanosoma brucei for which structures have been reported. Comparisons indicate that the key residues in the active site are highly conserved, as are the interactions with the cofactor and the product ribulose 5-phosphate. However, there are differences in the conformation of the substrate 6-phosphogluconate which may reflect distinct states relevant to catalysis. Analysis of the complex formed with the potent inhibitor 4-phospho-d-erythronohydroxamic acid, suggests that this molecule does indeed mimic the high-energy intermediate state that it was designed to. The analysis also identified, as a contaminant by-product of the inhibitor synthesis, 4-phospho-d-erythronamide, which binds in similar fashion. LlPDH can now serve as a model system for structure-based inhibitor design targeting the enzyme from Trypanosoma species.

==About this Structure==

Line 14:

[[Category: Phosphogluconate dehydrogenase (decarboxylating)]]

[[Category: Single protein]]

[[Category: Hunter, W.N.]]

[[Category: Hunter, W N.]]

[[Category: Iulek, J.]]

[[Category: Sundaramoorthy, R.]]

Line 25:

[[Category: pentose shunt]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Sun~~ Feb ~~3 10~~:39:46 2008''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:57:25 2008''

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 4: / Line 4: @@
 ==Overview==
-Crystal structures of recombinant Lactococcus lactis 6-phosphogluconate, dehydrogenase (LlPDH) in complex with substrate, cofactor, product and, inhibitors have been determined. LlPDH shares significant sequence, identity with the enzymes from sheep liver and the protozoan parasite, Trypanosoma brucei for which structures have been reported. Comparisons, indicate that the key residues in the active site are highly conserved, as, are the interactions with the cofactor and the product ribulose, 5-phosphate. However, there are differences in the conformation of the, substrate 6-phosphogluconate which may reflect distinct states relevant to, catalysis. Analysis of the complex formed with the potent inhibitor, 4-phospho-d-erythronohydroxamic acid, suggests that this molecule does, indeed mimic the high-energy intermediate state that it was designed to., The analysis also identified, as a contaminant by-product of the inhibitor, synthesis, 4-phospho-d-erythronamide, which binds in similar fashion., LlPDH can now serve as a model system for structure-based inhibitor design, targeting the enzyme from Trypanosoma species.
+Crystal structures of recombinant Lactococcus lactis 6-phosphogluconate dehydrogenase (LlPDH) in complex with substrate, cofactor, product and inhibitors have been determined. LlPDH shares significant sequence identity with the enzymes from sheep liver and the protozoan parasite Trypanosoma brucei for which structures have been reported. Comparisons indicate that the key residues in the active site are highly conserved, as are the interactions with the cofactor and the product ribulose 5-phosphate. However, there are differences in the conformation of the substrate 6-phosphogluconate which may reflect distinct states relevant to catalysis. Analysis of the complex formed with the potent inhibitor 4-phospho-d-erythronohydroxamic acid, suggests that this molecule does indeed mimic the high-energy intermediate state that it was designed to. The analysis also identified, as a contaminant by-product of the inhibitor synthesis, 4-phospho-d-erythronamide, which binds in similar fashion. LlPDH can now serve as a model system for structure-based inhibitor design targeting the enzyme from Trypanosoma species.
 ==About this Structure==
@@ Line 14: / Line 14: @@
 [[Category: Phosphogluconate dehydrogenase (decarboxylating)]]
 [[Category: Single protein]]
-[[Category: Hunter, W.N.]]
+[[Category: Hunter, W N.]]
 [[Category: Iulek, J.]]
 [[Category: Sundaramoorthy, R.]]
@@ Line 25: / Line 25: @@
 [[Category: pentose shunt]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb  3 10:39:46 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:57:25 2008''