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PDBsum entry 1gq2

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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
1gq2
Jmol
Contents
Protein chains
(+ 10 more) 555 a.a. *
Ligands
NAP ×16
OXL ×16
Metals
_MN ×16
_CL ×33
_NA ×36
Waters ×1049
* Residue conservation analysis
PDB id:
1gq2
Name: Oxidoreductase
Title: Malic enzyme from pigeon liver
Structure: Malic enzyme. Chain: a, b, c, d, e, f, g, h, i, j, k, l, m, n, o, p. Engineered: yes. Other_details: NADP+, oxalate, mn2+
Source: Columba livia. Domestic pigeon. Organism_taxid: 8932. Organ: liver. Expressed in: escherichia coli. Expression_system_taxid: 469008.
Biol. unit: Tetramer (from PDB file)
Resolution:
2.50Å     R-factor:   0.210     R-free:   0.256
Authors: Z.Yang,H.Zhang,T.Liang
Key ref:
Z.Yang et al. (2002). Structural studies of the pigeon cytosolic NADP(+)-dependent malic enzyme. Protein Sci, 11, 332-341. PubMed id: 11790843 DOI: 10.1110/ps.38002
Date:
19-Nov-01     Release date:   23-May-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P40927  (MAOX_COLLI) -  NADP-dependent malic enzyme
Seq:
Struc:
 
Seq:
Struc:
557 a.a.
555 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.1.1.40  - Malate dehydrogenase (oxaloacetate-decarboxylating) (NADP(+)).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction:
1. (S)-malate + NADP+ = pyruvate + CO2 + NADPH
2. Oxaloacetate = pyruvate + CO2
(S)-malate
+
NADP(+)
Bound ligand (Het Group name = NAP)
corresponds exactly
=
pyruvate
Bound ligand (Het Group name = OXL)
matches with 71.00% similarity
+ CO(2)
+ NADPH
Oxaloacetate
= pyruvate
+ CO(2)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     oxidation-reduction process   2 terms 
  Biochemical function     oxidoreductase activity     7 terms  

 

 
    reference    
 
 
DOI no: 10.1110/ps.38002 Protein Sci 11:332-341 (2002)
PubMed id: 11790843  
 
 
Structural studies of the pigeon cytosolic NADP(+)-dependent malic enzyme.
Z.Yang, H.Zhang, H.C.Hung, C.C.Kuo, L.C.Tsai, H.S.Yuan, W.Y.Chou, G.G.Chang, L.Tong.
 
  ABSTRACT  
 
Malic enzymes are widely distributed in nature, and have important biological functions. They catalyze the oxidative decarboxylation of malate to produce pyruvate and CO(2) in the presence of divalent cations (Mg(2+), Mn(2+)). Most malic enzymes have a clear selectivity for the dinucleotide cofactor, being able to use either NAD(+) or NADP(+), but not both. Structural studies of the human mitochondrial NAD(+)-dependent malic enzyme established that malic enzymes belong to a new class of oxidative decarboxylases. Here we report the crystal structure of the pigeon cytosolic NADP(+)-dependent malic enzyme, in a closed form, in a quaternary complex with NADP(+), Mn(2+), and oxalate. This represents the first structural information on an NADP(+)-dependent malic enzyme. Despite the sequence conservation, there are large differences in several regions of the pigeon enzyme structure compared to the human enzyme. One region of such differences is at the binding site for the 2'-phosphate group of the NADP(+) cofactor, which helps define the cofactor selectivity of the enzymes. Specifically, the structural information suggests Lys362 may have an important role in the NADP(+) selectivity of the pigeon enzyme, confirming our earlier kinetic observations on the K362A mutant. Our structural studies also revealed differences in the organization of the tetramer between the pigeon and the human enzymes, although the pigeon enzyme still obeys 222 symmetry.
 
  Selected figure(s)  
 
Figure 3.
Fig. 3. A possible molecular mechanism for cofactor selectivity. (A) Stereo drawing showing the structure comparison between human m-NAD-ME (in cyan for carbon atoms) and pigeon c-NADP-ME (in green) near the 2`-phsophate of NADP+. (B) Alignment of ME sequences near the binding site for the 2`-phosphate group of NADP+. The cofactor dependence of the various malic enzymes is indicated. The Asp345:Arg354 ion-pair is shown in purple. (A) was created with Grasp (Nicholls et al. 1991).
Figure 4.
Fig. 4. The tetramer of the pigeon malic enzyme. (A) Schematic drawing showing the tetramer of the pigeon ME. The four monomers are given different colors. The dimer and the tetramer interfaces are labeled. (B) The interactions of the C-terminal tail in one molecule (shown as stick models in cyan) with the other dimer of the tetramer (shown as molecular surfaces colored green and yellow, with their C termini labeled with the letter "C"). (C-E). Detailed structure comparisons of residues 541-546, in the tetramer interface, between the pigeon (C) and the closed (D) and open (E) forms of the human malic enzymes. These residues are located in the tetramer interface, indicated by the red oval in (A). The twofold axis is indicated with the purple oval. (A) was created with Ribbons (Carson 1987), (B-E) were created with Grasp (Nicholls et al. 1991).
 
  The above figures are reprinted by permission from the Protein Society: Protein Sci (2002, 11, 332-341) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21037855 G.P.Laliotis, I.Bizelis, and E.Rogdakis (2010).
Comparative Approach of the de novo Fatty Acid Synthesis (Lipogenesis) between Ruminant and Non Ruminant Mammalian Species: From Biochemical Level to the Main Regulatory Lipogenic Genes.
  Curr Genomics, 11, 168-183.  
19091740 J.Y.Hsieh, and H.C.Hung (2009).
Engineering of the Cofactor Specificities and Isoform-specific Inhibition of Malic Enzyme.
  J Biol Chem, 284, 4536-4544.  
19236308 J.Y.Hsieh, J.H.Liu, Y.W.Fang, and H.C.Hung (2009).
Dual roles of Lys(57) at the dimer interface of human mitochondrial NAD(P)+-dependent malic enzyme.
  Biochem J, 420, 201-209.  
19416979 J.Y.Hsieh, S.H.Chen, and H.C.Hung (2009).
Functional roles of the tetramer organization of malic enzyme.
  J Biol Chem, 284, 18096-18105.  
18959763 J.Y.Hsieh, G.Y.Liu, and H.C.Hung (2008).
Influential factor contributing to the isoform-specific inhibition by ATP of human mitochondrial NAD(P)+-dependent malic enzyme: functional roles of the nucleotide binding site Lys346.
  FEBS J, 275, 5383-5392.  
18020963 W.Ying (2008).
NAD(+)/NADH and NADP(+)/NADPH in Cellular Functions and Cell Death: Regulation and Biological Consequences.
  Antioxid Redox Signal, 10, 179-206.  
17557829 F.P.Bologna, C.S.Andreo, and M.F.Drincovich (2007).
Escherichia coli malic enzymes: two isoforms with substantial differences in kinetic properties, metabolic regulation, and structure.
  J Bacteriol, 189, 5937-5946.  
17704184 H.C.Chang, L.Y.Chen, Y.H.Lu, M.Y.Li, Y.H.Chen, C.H.Lin, and G.G.Chang (2007).
Metal ions stabilize a dimeric molten globule state between the open and closed forms of malic enzyme.
  Biophys J, 93, 3977-3988.  
16889632 S.C.Chang, K.Y.Lin, Y.J.Chen, C.H.Lai, G.G.Chang, and W.Y.Chou (2006).
Critical roles of conserved carboxylic acid residues in pigeon cytosolic NADP+-dependent malic enzyme.
  FEBS J, 273, 4072-4081.  
16143603 T.J.Merritt, D.Duvernell, and W.F.Eanes (2005).
Natural and synthetic alleles provide complementary insights into the nature of selection acting on the Men polymorphism of Drosophila melanogaster.
  Genetics, 171, 1707-1718.  
  15876562 W.Fukuda, Y.S.Ismail, T.Fukui, H.Atomi, and T.Imanaka (2005).
Characterization of an archaeal malic enzyme from the hyperthermophilic archaeon Thermococcus kodakaraensis KOD1.
  Archaea, 1, 293-301.  
14747989 C.W.Kuo, H.C.Hung, L.Tong, and G.G.Chang (2004).
Metal-Induced reversible structural interconversion of human mitochondrial NAD(P)+-dependent malic enzyme.
  Proteins, 54, 404-411.  
15604667 M.Saigo, F.P.Bologna, V.G.Maurino, E.Detarsio, C.S.Andreo, and M.F.Drincovich (2004).
Maize recombinant non-C4 NADP-malic enzyme: a novel dimeric malic enzyme with high specific activity.
  Plant Mol Biol, 55, 97.  
14596586 G.G.Chang, and L.Tong (2003).
Structure and function of malic enzymes, a new class of oxidative decarboxylases.
  Biochemistry, 42, 12721-12733.  
12962632 X.Tao, Z.Yang, and L.Tong (2003).
Crystal structures of substrate complexes of malic enzyme and insights into the catalytic mechanism.
  Structure, 11, 1141-1150.
PDB codes: 1pj2 1pj3 1pj4
12121650 Z.Yang, C.W.Lanks, and L.Tong (2002).
Molecular mechanism for the regulation of human mitochondrial NAD(P)+-dependent malic enzyme by ATP and fumarate.
  Structure, 10, 951-960.
PDB codes: 1gz3 1gz4
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 codes are shown on the right.