1b57: Difference between revisions

Revision as of 12:51, 21 February 2008

CLASS II FRUCTOSE-1,6-BISPHOSPHATE ALDOLASE IN COMPLEX WITH PHOSPHOGLYCOLOHYDROXAMATE

OverviewOverview

The structure of a class II fructose-1,6-bisphosphate aldolase in complex with the substrate analogue and inhibitor phosphoglycolohydroxamate (PGH) has been determined using X-ray diffraction terms to a resolution of 2.0 A (1 A=0.1 nm). The crystals are trigonal, space group P3121 with a=b=78.24 A, c=289.69 A. The asymmetric unit is a homodimer of (alpha/beta)8 barrels and the model has refined to give R-work 19.2 %, R-free (based on 5 % of the data) 23.0 %. PGH resembles the ene-diolate transition state of the physiological substrate dihydroxyacetone phosphate. It is well ordered and bound in a deep polar cavity at the C-terminal end of the (alpha/beta)8 barrel, where it chelates the catalytic zinc ion using hydroxyl and enolate oxygen atoms. Trigonal bipyramidal coordination of the zinc ion is completed by three histidine residues. The complex network of hydrogen bonds at the catalytic centre is required to organise the position of key functional groups and metal ion ligands. A well-defined monovalent cation-binding site is observed following significant re-organisation of loop structures. This assists the formation of a phosphate-binding site on one side of the barrel that tethers PGH in the catalytic site. The positions of functional groups of substrate and putative interactions with key amino acid residues are identified. Knowledge of the complex structure complements the results of spectroscopic and site-directed mutagenesis studies, and contributes to our understanding of the mechanism and substrate specificity of this family of enzymes. A reaction mechanism distinct from that proposed for other class II aldolases is discussed. The results suggest that the class II aldolases should be sub-divided into two groups on the basis of both distinct folds and mechanism.

About this StructureAbout this Structure

1B57 is a Single protein structure of sequence from Escherichia coli with , , and as ligands. Active as Fructose-bisphosphate aldolase, with EC number 4.1.2.13 Full crystallographic information is available from OCA.

ReferenceReference

The crystal structure of Escherichia coli class II fructose-1, 6-bisphosphate aldolase in complex with phosphoglycolohydroxamate reveals details of mechanism and specificity., Hall DR, Leonard GA, Reed CD, Watt CI, Berry A, Hunter WN, J Mol Biol. 1999 Mar 26;287(2):383-94. PMID:10080900

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-[[Image:1b57.gif|left|200px]]<br /><applet load="1b57" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1b57.gif|left|200px]]<br /><applet load="1b57" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1b57, resolution 2.0&Aring;" />
 '''CLASS II FRUCTOSE-1,6-BISPHOSPHATE ALDOLASE IN COMPLEX WITH PHOSPHOGLYCOLOHYDROXAMATE'''<br />
 ==Overview==
-The structure of a class II fructose-1,6-bisphosphate aldolase in complex, with the substrate analogue and inhibitor phosphoglycolohydroxamate (PGH), has been determined using X-ray diffraction terms to a resolution of 2.0 A, (1 A=0.1 nm). The crystals are trigonal, space group P3121 with a=b=78.24, A, c=289.69 A. The asymmetric unit is a homodimer of (alpha/beta)8 barrels, and the model has refined to give R-work 19.2 %, R-free (based on 5 % of, the data) 23.0 %. PGH resembles the ene-diolate transition state of the, physiological substrate dihydroxyacetone phosphate. It is well ordered and, bound in a deep polar cavity at the C-terminal end of the (alpha/beta)8, barrel, where it chelates the catalytic zinc ion using hydroxyl and, enolate oxygen atoms. Trigonal bipyramidal coordination of the zinc ion is, completed by three histidine residues. The complex network of hydrogen, bonds at the catalytic centre is required to organise the position of key, functional groups and metal ion ligands. A well-defined monovalent, cation-binding site is observed following significant re-organisation of, loop structures. This assists the formation of a phosphate-binding site on, one side of the barrel that tethers PGH in the catalytic site. The, positions of functional groups of substrate and putative interactions with, key amino acid residues are identified. Knowledge of the complex structure, complements the results of spectroscopic and site-directed mutagenesis, studies, and contributes to our understanding of the mechanism and, substrate specificity of this family of enzymes. A reaction mechanism, distinct from that proposed for other class II aldolases is discussed. The, results suggest that the class II aldolases should be sub-divided into two, groups on the basis of both distinct folds and mechanism.
+The structure of a class II fructose-1,6-bisphosphate aldolase in complex with the substrate analogue and inhibitor phosphoglycolohydroxamate (PGH) has been determined using X-ray diffraction terms to a resolution of 2.0 A (1 A=0.1 nm). The crystals are trigonal, space group P3121 with a=b=78.24 A, c=289.69 A. The asymmetric unit is a homodimer of (alpha/beta)8 barrels and the model has refined to give R-work 19.2 %, R-free (based on 5 % of the data) 23.0 %. PGH resembles the ene-diolate transition state of the physiological substrate dihydroxyacetone phosphate. It is well ordered and bound in a deep polar cavity at the C-terminal end of the (alpha/beta)8 barrel, where it chelates the catalytic zinc ion using hydroxyl and enolate oxygen atoms. Trigonal bipyramidal coordination of the zinc ion is completed by three histidine residues. The complex network of hydrogen bonds at the catalytic centre is required to organise the position of key functional groups and metal ion ligands. A well-defined monovalent cation-binding site is observed following significant re-organisation of loop structures. This assists the formation of a phosphate-binding site on one side of the barrel that tethers PGH in the catalytic site. The positions of functional groups of substrate and putative interactions with key amino acid residues are identified. Knowledge of the complex structure complements the results of spectroscopic and site-directed mutagenesis studies, and contributes to our understanding of the mechanism and substrate specificity of this family of enzymes. A reaction mechanism distinct from that proposed for other class II aldolases is discussed. The results suggest that the class II aldolases should be sub-divided into two groups on the basis of both distinct folds and mechanism.
 ==About this Structure==
-B57 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with ZN, NA, CL and PGH as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Fructose-bisphosphate_aldolase Fructose-bisphosphate aldolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.2.13 4.1.2.13] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1B57 OCA].
+B57 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=NA:'>NA</scene>, <scene name='pdbligand=CL:'>CL</scene> and <scene name='pdbligand=PGH:'>PGH</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Fructose-bisphosphate_aldolase Fructose-bisphosphate aldolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.2.13 4.1.2.13] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1B57 OCA].
 ==Reference==
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 [[Category: Fructose-bisphosphate aldolase]]
 [[Category: Single protein]]
-[[Category: Hall, D.R.]]
+[[Category: Hall, D R.]]
-[[Category: Hunter, W.N.]]
+[[Category: Hunter, W N.]]
 [[Category: CL]]
 [[Category: NA]]
@@ Line 24: / Line 24: @@
 [[Category: lyase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 11:22:16 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:51:38 2008''