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PDBsum entry 2r46

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
2r46
Jmol
Contents
Protein chains
495 a.a. *
Ligands
EDO ×22
T3A ×2
FAD ×2
PEP ×2
BOG ×5
IMD
Waters ×385
* Residue conservation analysis
PDB id:
2r46
Name: Oxidoreductase
Title: Crystal structure of escherichia coli glycerol-3-phosphate dehydrogenase in complex with 2-phosphopyruvic acid.
Structure: Aerobic glycerol-3-phosphate dehydrogenase. Chain: a, b. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Gene: glpd, glyd. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
2.10Å     R-factor:   0.193     R-free:   0.230
Authors: J.I.Yeh,S.Du,U.Chinte
Key ref:
J.I.Yeh et al. (2008). Structure of glycerol-3-phosphate dehydrogenase, an essential monotopic membrane enzyme involved in respiration and metabolism. Proc Natl Acad Sci U S A, 105, 3280-3285. PubMed id: 18296637 DOI: 10.1073/pnas.0712331105
Date:
30-Aug-07     Release date:   29-Apr-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P13035  (GLPD_ECOLI) -  Aerobic glycerol-3-phosphate dehydrogenase
Seq:
Struc:
501 a.a.
495 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.1.5.3  - Glycerol-3-phosphate dehydrogenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: sn-glycerol 3-phosphate + a quinone = glycerone phosphate + a quinol
sn-glycerol 3-phosphate
Bound ligand (Het Group name = PEP)
matches with 66.00% similarity
+
quinone
Bound ligand (Het Group name = BOG)
matches with 40.00% similarity
= glycerone phosphate
+ quinol
      Cofactor: Flavin
Flavin
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   3 terms 
  Biological process     oxidation-reduction process   5 terms 
  Biochemical function     electron carrier activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1073/pnas.0712331105 Proc Natl Acad Sci U S A 105:3280-3285 (2008)
PubMed id: 18296637  
 
 
Structure of glycerol-3-phosphate dehydrogenase, an essential monotopic membrane enzyme involved in respiration and metabolism.
J.I.Yeh, U.Chinte, S.Du.
 
  ABSTRACT  
 
Sn-glycerol-3-phosphate dehydrogenase (GlpD) is an essential membrane enzyme, functioning at the central junction of respiration, glycolysis, and phospholipid biosynthesis. Its critical role is indicated by the multitiered regulatory mechanisms that stringently controls its expression and function. Once expressed, GlpD activity is regulated through lipid-enzyme interactions in Escherichia coli. Here, we report seven previously undescribed structures of the fully active E. coli GlpD, up to 1.75 A resolution. In addition to elucidating the structure of the native enzyme, we have determined the structures of GlpD complexed with substrate analogues phosphoenolpyruvate, glyceric acid 2-phosphate, glyceraldehyde-3-phosphate, and product, dihydroxyacetone phosphate. These structural results reveal conformational states of the enzyme, delineating the residues involved in substrate binding and catalysis at the glycerol-3-phosphate site. Two probable mechanisms for catalyzing the dehydrogenation of glycerol-3-phosphate are envisioned, based on the conformational states of the complexes. To further correlate catalytic dehydrogenation to respiration, we have additionally determined the structures of GlpD bound with ubiquinone analogues menadione and 2-n-heptyl-4-hydroxyquinoline N-oxide, identifying a hydrophobic plateau that is likely the ubiquinone-binding site. These structures illuminate probable mechanisms of catalysis and suggest how GlpD shuttles electrons into the respiratory pathway. Glycerol metabolism has been implicated in insulin signaling and perturbations in glycerol uptake and catabolism are linked to obesity in humans. Homologs of GlpD are found in practically all organisms, from prokaryotes to humans, with >45% consensus protein sequences, signifying that these structural results on the prokaryotic enzyme may be readily applied to the eukaryotic GlpD enzymes.
 
  Selected figure(s)  
 
Figure 1.
Schematic of the glycerol metabolic pathway in E. coli. Protein members of the glycerol metabolic pathway includes glycerol facilitator (GlpF/AQP), a member of the aquaporin family of major intrinsic proteins. The soluble glycerol kinase (GK) phosphorylates glycerol to G3P. Another membrane protein constituent of this pathway is the transporter for the uptake of G3P (GlpT) with concomitant exit of Pi. Oxidation of G3P to DHAP is catalyzed by the monotopic membrane enzyme, glycerol-3-phosphate dehydrogenase (GlpD), a primary dehydrogenase. Concurrent with oxidation of G3P is reduction of flavin adenine dinucleotide (FAD) to FADH[2], which passes on electrons to ubiquinone (UQ) forming the reduced form (UQH[2]) and ultimately shuttling electrons to oxygen or nitrate.
Figure 4.
Reaction scheme. Schematic diagram showing the active site with G3P, modeled from the GAP-complex structure. Only selected interactions in the active site are shown. Dotted lines indicate distances, in angstroms, between atoms in proximity for hydrogen bonding interactions. For FAD, only the isoalloxazine ring is depicted.
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20025846 E.A.Berry, L.S.Huang, D.W.Lee, F.Daldal, K.Nagai, and N.Minagawa (2010).
Ascochlorin is a novel, specific inhibitor of the mitochondrial cytochrome bc1 complex.
  Biochim Biophys Acta, 1797, 360-370.
PDB code: 3h1l
21110891 H.C.Tseng, C.L.Harwell, C.H.Martin, and K.L.Prather (2010).
Biosynthesis of chiral 3-hydroxyvalerate from single propionate-unrelated carbon sources in metabolically engineered E. coli.
  Microb Cell Fact, 9, 96.  
20667175 K.R.Vinothkumar, and R.Henderson (2010).
Structures of membrane proteins.
  Q Rev Biophys, 43, 65.  
19767390 H.M.Eriksson, P.Wessman, C.Ge, K.Edwards, and A.Wieslander (2009).
Massive formation of intracellular membrane vesicles in Escherichia coli by a monotopic membrane-bound lipid glycosyltransferase.
  J Biol Chem, 284, 33904-33914.  
19487671 M.Marcia, U.Ermler, G.Peng, and H.Michel (2009).
The structure of Aquifex aeolicus sulfide:quinone oxidoreductase, a basis to understand sulfide detoxification and respiration.
  Proc Natl Acad Sci U S A, 106, 9625-9630.
PDB codes: 3h27 3h28 3h29 3hyv 3hyw 3hyx
18663026 M.Giladi, Y.Porat, A.Blatt, Y.Wasserman, E.D.Kirson, E.Dekel, and Y.Palti (2008).
Microbial growth inhibition by alternating electric fields.
  Antimicrob Agents Chemother, 52, 3517-3522.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.