1gdh: Difference between revisions

Revision as of 13:48, 21 February 2008

CRYSTAL STRUCTURE OF A NAD-DEPENDENT D-GLYCERATE DEHYDROGENASE AT 2.4 ANGSTROMS RESOLUTION

OverviewOverview

D-Glycerate dehydrogenase (GDH) catalyzes the NADH-linked reduction of hydroxypyruvate to D-glycerate. GDH is a member of a family of NAD-dependent dehydrogenases that is characterized by a specificity for the D-isomer of the hydroxyacid substrate. The crystal structure of the apoenzyme form of GDH from Hyphomicrobium methylovorum has been determined by the method of isomorphous replacement and refined at 2.4 A resolution using a restrained least-squares method. The crystallographic R-factor is 19.4% for all 24,553 measured reflections between 10.0 and 2.4 A resolution. The GDH molecule is a symmetrical dimer composed of subunits of molecular mass 38,000, and shares significant structural homology with another NAD-dependent enzyme, formate dehydrogenase. The GDH subunit consists of two structurally similar domains that are approximately related to each other by 2-fold symmetry. The domains are separated by a deep cleft that forms the putative NAD and substrate binding sites. One of the domains has been identified as the NAD-binding domain based on its close structural similarity to the NAD-binding domains of other NAD-dependent dehydrogenases. The topology of the second domain is different from that found in the various catalytic domains of other dehydrogenases. A model of a ternary complex of GDH has been built in which putative catalytic residues are identified based on sequence homology between the D-isomer specific dehydrogenases. A structural comparison between GDH and L-lactate dehydrogenase indicates a convergence of active site residues and geometries for these two enzymes. The reactions catalyzed are chemically equivalent but of opposing stereospecificity. A hypothesis is presented to explain how the two enzymes may exploit the same coenzyme stereochemistry and a similar spatial arrangement of catalytic residues to carry out reactions that proceed to opposite enantiomers.

About this StructureAbout this Structure

1GDH is a Single protein structure of sequence from Hyphomicrobium methylovorum with as ligand. Active as Glycerate dehydrogenase, with EC number 1.1.1.29 Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure of a NAD-dependent D-glycerate dehydrogenase at 2.4 A resolution., Goldberg JD, Yoshida T, Brick P, J Mol Biol. 1994 Mar 4;236(4):1123-40. PMID:8120891

Page seeded by OCA on Thu Feb 21 12:48:53 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:1gdh.gif|left|200px]]<br /><applet load="1gdh" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1gdh.gif|left|200px]]<br /><applet load="1gdh" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1gdh, resolution 2.4&Aring;" />
 '''CRYSTAL STRUCTURE OF A NAD-DEPENDENT D-GLYCERATE DEHYDROGENASE AT 2.4 ANGSTROMS RESOLUTION'''<br />
 ==Overview==
-D-Glycerate dehydrogenase (GDH) catalyzes the NADH-linked reduction of, hydroxypyruvate to D-glycerate. GDH is a member of a family of, NAD-dependent dehydrogenases that is characterized by a specificity for, the D-isomer of the hydroxyacid substrate. The crystal structure of the, apoenzyme form of GDH from Hyphomicrobium methylovorum has been determined, by the method of isomorphous replacement and refined at 2.4 A resolution, using a restrained least-squares method. The crystallographic R-factor is, 19.4% for all 24,553 measured reflections between 10.0 and 2.4 A, resolution. The GDH molecule is a symmetrical dimer composed of subunits, of molecular mass 38,000, and shares significant structural homology with, another NAD-dependent enzyme, formate dehydrogenase. The GDH subunit, consists of two structurally similar domains that are approximately, related to each other by 2-fold symmetry. The domains are separated by a, deep cleft that forms the putative NAD and substrate binding sites. One of, the domains has been identified as the NAD-binding domain based on its, close structural similarity to the NAD-binding domains of other, NAD-dependent dehydrogenases. The topology of the second domain is, different from that found in the various catalytic domains of other, dehydrogenases. A model of a ternary complex of GDH has been built in, which putative catalytic residues are identified based on sequence, homology between the D-isomer specific dehydrogenases. A structural, comparison between GDH and L-lactate dehydrogenase indicates a convergence, of active site residues and geometries for these two enzymes. The, reactions catalyzed are chemically equivalent but of opposing, stereospecificity. A hypothesis is presented to explain how the two, enzymes may exploit the same coenzyme stereochemistry and a similar, spatial arrangement of catalytic residues to carry out reactions that, proceed to opposite enantiomers.
+D-Glycerate dehydrogenase (GDH) catalyzes the NADH-linked reduction of hydroxypyruvate to D-glycerate. GDH is a member of a family of NAD-dependent dehydrogenases that is characterized by a specificity for the D-isomer of the hydroxyacid substrate. The crystal structure of the apoenzyme form of GDH from Hyphomicrobium methylovorum has been determined by the method of isomorphous replacement and refined at 2.4 A resolution using a restrained least-squares method. The crystallographic R-factor is 19.4% for all 24,553 measured reflections between 10.0 and 2.4 A resolution. The GDH molecule is a symmetrical dimer composed of subunits of molecular mass 38,000, and shares significant structural homology with another NAD-dependent enzyme, formate dehydrogenase. The GDH subunit consists of two structurally similar domains that are approximately related to each other by 2-fold symmetry. The domains are separated by a deep cleft that forms the putative NAD and substrate binding sites. One of the domains has been identified as the NAD-binding domain based on its close structural similarity to the NAD-binding domains of other NAD-dependent dehydrogenases. The topology of the second domain is different from that found in the various catalytic domains of other dehydrogenases. A model of a ternary complex of GDH has been built in which putative catalytic residues are identified based on sequence homology between the D-isomer specific dehydrogenases. A structural comparison between GDH and L-lactate dehydrogenase indicates a convergence of active site residues and geometries for these two enzymes. The reactions catalyzed are chemically equivalent but of opposing stereospecificity. A hypothesis is presented to explain how the two enzymes may exploit the same coenzyme stereochemistry and a similar spatial arrangement of catalytic residues to carry out reactions that proceed to opposite enantiomers.
 ==About this Structure==
-GDH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Hyphomicrobium_methylovorum Hyphomicrobium methylovorum] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Glycerate_dehydrogenase Glycerate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.29 1.1.1.29] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1GDH OCA].
+GDH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Hyphomicrobium_methylovorum Hyphomicrobium methylovorum] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Glycerate_dehydrogenase Glycerate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.29 1.1.1.29] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GDH OCA].
 ==Reference==
@@ Line 15: / Line 15: @@
 [[Category: Single protein]]
 [[Category: Brick, P.]]
-[[Category: Goldberg, J.D.]]
+[[Category: Goldberg, J D.]]
 [[Category: Yoshida, T.]]
 [[Category: SO4]]
 [[Category: oxidoreductase(choh (d)-nad(p)+ (a))]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 15:57:54 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:48:53 2008''