PDBsum entry 1pl6

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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
Jmol PyMol
Protein chain
356 a.a. *
NAD ×4
572 ×4
_ZN ×4
Waters ×1213
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Human sdh/nadh/inhibitor complex
Structure: Sorbitol dehydrogenase. Chain: a, b, c, d. Synonym: l-iditol 2-dehydrogenase. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Tetramer (from PDB file)
2.00Å     R-factor:   0.183     R-free:   0.211
Authors: T.A.Pauly,J.L.Ekstrom,D.A.Beebe,B.Chrunyk,D.Cunningham,M.Gri A.Kamath,S.E.Lee,R.Madura,D.Mcguire,T.Subashi,D.Wasilko,P.W B.L.Mylari,P.J.Oates,P.D.Adams,V.L.Rath
Key ref:
T.A.Pauly et al. (2003). X-ray crystallographic and kinetic studies of human sorbitol dehydrogenase. Structure, 11, 1071-1085. PubMed id: 12962626 DOI: 10.1016/S0969-2126(03)00167-9
07-Jun-03     Release date:   17-Feb-04    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q00796  (DHSO_HUMAN) -  Sorbitol dehydrogenase
357 a.a.
356 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - L-iditol 2-dehydrogenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: L-iditol + NAD+ = L-sorbose + NADH
Bound ligand (Het Group name = NAD)
corresponds exactly
= L-sorbose
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular space   9 terms 
  Biological process     oxidation-reduction process   15 terms 
  Biochemical function     oxidoreductase activity     8 terms  


DOI no: 10.1016/S0969-2126(03)00167-9 Structure 11:1071-1085 (2003)
PubMed id: 12962626  
X-ray crystallographic and kinetic studies of human sorbitol dehydrogenase.
T.A.Pauly, J.L.Ekstrom, D.A.Beebe, B.Chrunyk, D.Cunningham, M.Griffor, A.Kamath, S.E.Lee, R.Madura, D.Mcguire, T.Subashi, D.Wasilko, P.Watts, B.L.Mylari, P.J.Oates, P.D.Adams, V.L.Rath.
Sorbitol dehydrogenase (hSDH) and aldose reductase form the polyol pathway that interconverts glucose and fructose. Redox changes from overproduction of the coenzyme NADH by SDH may play a role in diabetes-induced dysfunction in sensitive tissues, making SDH a therapeutic target for diabetic complications. We have purified and determined the crystal structures of human SDH alone, SDH with NAD(+), and SDH with NADH and an inhibitor that is competitive with fructose. hSDH is a tetramer of identical, catalytically active subunits. In the apo and NAD(+) complex, the catalytic zinc is coordinated by His69, Cys44, Glu70, and a water molecule. The inhibitor coordinates the zinc through an oxygen and a nitrogen atom with the concomitant dissociation of Glu70. The inhibitor forms hydrophobic interactions to NADH and likely sterically occludes substrate binding. The structure of the inhibitor complex provides a framework for developing more potent inhibitors of hSDH.
  Selected figure(s)  
Figure 5.
Figure 5. Binding Site of Inhibitor CP-166,572(A) Electron density for the inhibitor. Derived from a 2F[o] - F[c] omit map contoured at 1s above the mean.(B) CP-166,572 interacts with both Zn and NADH. Stereo image showing the simultaneous interaction between the inhibitor and the catalytic zinc as well as the nicotinamide ring of NADH. All other ligands to zinc are shown.(C) Binding site of CP-166,572. Stereo image showing importance of hydrophobic contacts in binding inhibitor. All residues (gray carbon atoms) within van der Waals distance to CP-166,572 (green carbon atoms) are shown. Only a single direct hydrogen bond is formed to the enzyme (to Glu155); all other hydrogen bonds are formed to water molecules (red spheres).
  The above figure is reprinted by permission from Cell Press: Structure (2003, 11, 1071-1085) copyright 2003.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21543846 H.Yennawar, M.Møller, R.Gillilan, and N.Yennawar (2011).
X-ray crystal structure and small-angle X-ray scattering of sheep liver sorbitol dehydrogenase.
  Acta Crystallogr D Biol Crystallogr, 67, 440-446.
PDB code: 3qe3
20835842 S.Porté, A.Moeini, I.Reche, N.Shafqat, U.Oppermann, J.Farrés, and X.Parés (2011).
Kinetic and structural evidence of the alkenal/one reductase specificity of human ΞΆ-crystallin.
  Cell Mol Life Sci, 68, 1065-1077.  
20414651 B.Kim, R.P.Sullivan, and H.Zhao (2010).
Cloning, characterization, and engineering of fungal L-arabinitol dehydrogenases.
  Appl Microbiol Biotechnol, 87, 1407-1414.  
20979641 J.Hedlund, H.Jörnvall, and B.Persson (2010).
Subdivision of the MDR superfamily of medium-chain dehydrogenases/reductases through iterative hidden Markov model refinement.
  BMC Bioinformatics, 11, 534.  
20177886 M.K.Tiwari, H.J.Moon, M.Jeya, and J.K.Lee (2010).
Cloning and characterization of a thermostable xylitol dehydrogenase from Rhizobium etli CFN42.
  Appl Microbiol Biotechnol, 87, 571-581.  
19674460 L.Rutten, C.Ribot, B.Trejo-Aguilar, H.A.Wösten, and Vries (2009).
A single amino acid change (Y318F) in the L-arabitol dehydrogenase (LadA) from Aspergillus niger results in a significant increase in affinity for D-sorbitol.
  BMC Microbiol, 9, 166.  
19131516 P.J.Baker, K.L.Britton, M.Fisher, J.Esclapez, C.Pire, M.J.Bonete, J.Ferrer, and D.W.Rice (2009).
Active site dynamics in the zinc-dependent medium chain alcohol dehydrogenase superfamily.
  Proc Natl Acad Sci U S A, 106, 779-784.
PDB codes: 2vwg 2vwh 2vwp 2vwq
18074158 A.Krezel, and W.Maret (2008).
Thionein/metallothionein control Zn(II) availability and the activity of enzymes.
  J Biol Inorg Chem, 13, 401-409.  
19011751 B.Persson, J.Hedlund, and H.Jörnvall (2008).
Medium- and short-chain dehydrogenase/reductase gene and protein families : the MDR superfamily.
  Cell Mol Life Sci, 65, 3879-3894.  
18566893 Sousa, M.d.e.l. .G.Paniago, P.Arruda, and J.A.Yunes (2008).
Sugar levels modulate sorbitol dehydrogenase expression in maize.
  Plant Mol Biol, 68, 203-213.  
18097725 Z.B.Li, Z.Wu, Q.Cao, D.W.Dick, J.R.Tseng, S.S.Gambhir, and X.Chen (2008).
The synthesis of 18F-FDS and its potential application in molecular imaging.
  Mol Imaging Biol, 10, 92-98.  
17938906 R.Sullivan, and H.Zhao (2007).
Cloning, characterization, and mutational analysis of a highly active and stable L-arabinitol 4-dehydrogenase from Neurospora crassa.
  Appl Microbiol Biotechnol, 77, 845-852.  
16556607 C.C.Milburn, H.J.Lamble, A.Theodossis, S.D.Bull, D.W.Hough, M.J.Danson, and G.L.Taylor (2006).
The structural basis of substrate promiscuity in glucose dehydrogenase from the hyperthermophilic archaeon Sulfolobus solfataricus.
  J Biol Chem, 281, 14796-14804.
PDB codes: 2cd9 2cda 2cdb 2cdc
16896602 L.H.Lima, C.G.Pinheiro, Moraes, Freitas, and F.A.Torres (2006).
Xylitol dehydrogenase from Candida tropicalis: molecular cloning of the gene and structural analysis of the protein.
  Appl Microbiol Biotechnol, 73, 631-639.  
15623532 S.Watanabe, T.Kodaki, and K.Makino (2005).
Complete reversal of coenzyme specificity of xylitol dehydrogenase and increase of thermostability by the introduction of structural zinc.
  J Biol Chem, 280, 10340-10349.  
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.