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PDBsum entry 1n1e

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
1n1e
Jmol
Contents
Protein chains
349 a.a. *
Ligands
NDE ×2
Waters ×306
* Residue conservation analysis
PDB id:
1n1e
Name: Oxidoreductase
Title: Crystal structure of leishmania mexicana glycerol-3- phosphate dehydrogenase complexed with dhap and NAD
Structure: Glycerol-3-phosphate dehydrogenase. Chain: a, b. Engineered: yes
Source: Leishmania mexicana. Organism_taxid: 5665. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dimer (from PQS)
Resolution:
1.90Å     R-factor:   0.174     R-free:   0.195
Authors: J.Choe,W.G.J.Hol
Key ref:
J.Choe et al. (2003). Leishmania mexicana glycerol-3-phosphate dehydrogenase showed conformational changes upon binding a bi-substrate adduct. J Mol Biol, 329, 335-349. PubMed id: 12758080 DOI: 10.1016/S0022-2836(03)00421-2
Date:
17-Oct-02     Release date:   27-May-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P90551  (GPDA_LEIME) -  Glycerol-3-phosphate dehydrogenase [NAD(+)], glycosomal
Seq:
Struc:
366 a.a.
349 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.1.1.8  - Glycerol-3-phosphate dehydrogenase (NAD(+)).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: sn-glycerol 3-phosphate + NAD+ = glycerone phosphate + NADH
sn-glycerol 3-phosphate
+
NAD(+)
Bound ligand (Het Group name = NDE)
matches with 81.00% similarity
= glycerone phosphate
+ NADH
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   4 terms 
  Biological process     oxidation-reduction process   4 terms 
  Biochemical function     oxidoreductase activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1016/S0022-2836(03)00421-2 J Mol Biol 329:335-349 (2003)
PubMed id: 12758080  
 
 
Leishmania mexicana glycerol-3-phosphate dehydrogenase showed conformational changes upon binding a bi-substrate adduct.
J.Choe, D.Guerra, P.A.Michels, W.G.Hol.
 
  ABSTRACT  
 
Certain pathogenic trypanosomatids are highly dependent on glycolysis for ATP production, and hence their glycolytic enzymes, including glycerol-3-phosphate dehydrogenase (GPDH), are considered attractive drug targets. The ternary complex structure of Leishmania mexicana GPDH (LmGPDH) with dihydroxyacetone phosphate (DHAP) and NAD(+) was determined to 1.9A resolution as a further step towards understanding this enzyme's mode of action. When compared with the apo and binary complex structures, the ternary complex structure shows an 11 degrees hinge-bending motion of the C-terminal domain with respect to the N-terminal domain. In addition, residues in the C-terminal domain involved in catalysis or substrates binding show significant movements and a previously invisible five-residue loop region becomes well ordered and participates in NAD(+) binding. Unexpectedly, DHAP and NAD(+) appear to form a covalent bond, producing an adduct in the active site of LmGPDH. Modeling a ternary complex glycerol 3-phosphate (G3P) and NAD(+) with LmGPDH identified ten active site residues that are highly conserved among all GPDHs. Two lysine residues, Lys125 and Lys210, that are presumed to be critical in catalysis, were mutated resulting in greatly reduced catalytic activity. Comparison with other structurally related enzymes found by the program DALI suggested Lys210 as a key catalytic residue, which is located on a structurally conserved alpha-helix. From the results of site-directed mutagenesis, molecular modeling and comparison with related dehydrogenases, a catalytic mechanism of LmGPDH and a possible evolutionary scenario of this group of dehydrogenases are proposed.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Superposition of apo (green) and ternary (red) LmGPDH structures (a) using the N-terminal domain for superposition and side-chain residues that interact with the substrates are shown; (b) using the N-terminal domain for superposition and only side-chain residues from the N-terminal domain are shown; (c) using the C-terminal domain for superposition and only side-chain residues from the C-terminal domain are drawn.
Figure 9.
Figure 9. Proposed catalytic mechanism of LmGPDH for (a) the oxidation of G3P to DHAP and (b) the formation of the adduct from DHAP and NAD^+.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2003, 329, 335-349) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
18848533 S.A.Krupenko (2009).
FDH: an aldehyde dehydrogenase fusion enzyme in folate metabolism.
  Chem Biol Interact, 178, 84-93.  
17640270 K.Figarella, N.L.Uzcategui, Y.Zhou, A.LeFurgey, M.Ouellette, H.Bhattacharjee, and R.Mukhopadhyay (2007).
Biochemical characterization of Leishmania major aquaglyceroporin LmAQP1: possible role in volume regulation and osmotaxis.
  Mol Microbiol, 65, 1006-1017.  
15557260 S.Sakasegawa, C.H.Hagemeier, R.K.Thauer, L.O.Essen, and S.Shima (2004).
Structural and functional analysis of the gpsA gene product of Archaeoglobus fulgidus: a glycerol-3-phosphate dehydrogenase with an unusual NADP+ preference.
  Protein Sci, 13, 3161-3171.
PDB code: 1txg
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