PDBsum entry 2r24

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Oxidoreductase PDB id
Jmol PyMol
Protein chain
316 a.a. *
Waters ×285
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Human aldose reductase structure
Structure: Aldose reductase. Chain: a. Synonym: ar, aldehyde reductase. Ec:
Source: Homo sapiens. Human. Organism_taxid: 9606
1.75Å     R-factor:   0.132     R-free:   0.166
Authors: M.P.Blakeley,F.Ruiz,R.Cachau,I.Hazemann,F.Meilleur,A.Mitschl S.Ginell,P.Afonine,O.N.Ventura,A.Cousido-Siah,M.Haertlein, A.Joachimiak,D.Myles,A.Podjarny
Key ref:
M.P.Blakeley et al. (2008). Quantum model of catalysis based on a mobile proton revealed by subatomic x-ray and neutron diffraction studies of h-aldose reductase. Proc Natl Acad Sci U S A, 105, 1844-1848. PubMed id: 18250329 DOI: 10.1073/pnas.0711659105
24-Aug-07     Release date:   23-Dec-08    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P15121  (ALDR_HUMAN) -  Aldose reductase
316 a.a.
316 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Aldehyde reductase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Alditol + NAD(P)(+) = aldose + NAD(P)H
Bound ligand (Het Group name = NAP)
matches with 82.76% similarity
= aldose
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular space   11 terms 
  Biological process     regulation of urine volume   27 terms 
  Biochemical function     electron carrier activity     5 terms  


DOI no: 10.1073/pnas.0711659105 Proc Natl Acad Sci U S A 105:1844-1848 (2008)
PubMed id: 18250329  
Quantum model of catalysis based on a mobile proton revealed by subatomic x-ray and neutron diffraction studies of h-aldose reductase.
M.P.Blakeley, F.Ruiz, R.Cachau, I.Hazemann, F.Meilleur, A.Mitschler, S.Ginell, P.Afonine, O.N.Ventura, A.Cousido-Siah, M.Haertlein, A.Joachimiak, D.Myles, A.Podjarny.
We present results of combined studies of the enzyme human aldose reductase (h-AR, 36 kDa) using single-crystal x-ray data (0.66 A, 100K; 0.80 A, 15K; 1.75 A, 293K), neutron Laue data (2.2 A, 293K), and quantum mechanical modeling. These complementary techniques unveil the internal organization and mobility of the hydrogen bond network that defines the properties of the catalytic engine, explaining how this promiscuous enzyme overcomes the simultaneous requirements of efficiency and promiscuity offering a general mechanistic view for this class of enzymes.
  Selected figure(s)  
Figure 1.
X-ray results. (A) Ribbon drawing of hydrogenated (S1) (red) and deuterated (S2) (blue) structures (rmsd = 0.7 Å), superposed with x-ray 2F [o]−F [c] density map (S2) structure, 1.5 rms magenta contours for the inhibitor IDD594. (B) Active-site conformation showing the residues around NADP^+ and inhibitor IDD594 for the deuterated structure (S2). (C) Closeup of Lys-77 and Asp-43 in deuterated h-AR superposed with the two difference maps [deuterated (S2), 2 rms blue contours; and hydrogenated (S1), 2 rms red contours]. These maps show the hydrogen atom in the H-bond Asp-43–Lys-77 in two alternative conformations. This shared partial protonation is indicated also by the bond lengths (corresponding to structure S2) in the carboxylate of Asp-43. The H-atom is placed on the Lys-77 side.
Figure 2.
Comparison of x-ray and neutron results. (A) X-ray model of fully deuterated h-AR-IDD594 complex [0.80-Å data collected at 15K, S2; treatment with HKL2000 (16); refinement with SHELX (17)] superposed with electron density difference map (F [o]−F [c], 2 rms blue contours, phases calculated from model without deuteriums). The map suggests partial deuteration of the Asp-43. The model shows the neutral state for the Asp-43-Lys-77 pair. (B) Model from joint x-ray/neutron refinement of fully deuterated h-AR-IDD594 complex (S3) (both data collected at room temperature) superposed with neutron scattering-density map calculated with phases from the model with all deuteriums (2F [o]−F [c], 2 rms red contours, 1 rms gold contours, S3). Note that the deuterium atom D (marked in magenta) was included in the model but is only weakly present in the map, confirming the partial protonation of the Asp-43-Lys-77 pair. (C) Closeup of B centered on the Lys-77 head. The map (2 rms red contours) shows strong density for only the two deuteriums marked in light gray.
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  20383004 M.M.Blum, S.J.Tomanicek, H.John, B.L.Hanson, H.Rüterjans, B.P.Schoenborn, P.Langan, and J.C.Chen (2010).
X-ray structure of perdeuterated diisopropyl fluorophosphatase (DFPase): perdeuteration of proteins for neutron diffraction.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 66, 379-385.
PDB code: 3kgg
20547071 R.Boyd, and A.Somogyi (2010).
The mobile proton hypothesis in fragmentation of protonated peptides: a perspective.
  J Am Soc Mass Spectrom, 21, 1275-1278.  
19765976 A.Joachimiak (2009).
High-throughput crystallography for structural genomics.
  Curr Opin Struct Biol, 19, 573-584.  
  19342793 I.Petit-Haertlein, M.P.Blakeley, E.Howard, I.Hazemann, A.Mitschler, M.Haertlein, and A.Podjarny (2009).
Perdeuteration, purification, crystallization and preliminary neutron diffraction of an ocean pout type III antifreeze protein.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 406-409.  
19465771 P.D.Adams, M.Mustyakimov, P.V.Afonine, and P.Langan (2009).
Generalized X-ray and neutron crystallographic analysis: more accurate and complete structures for biological macromolecules.
  Acta Crystallogr D Biol Crystallogr, 65, 567-573.  
19700309 P.D.Adams, P.V.Afonine, R.W.Grosse-Kunstleve, R.J.Read, J.S.Richardson, D.C.Richardson, and T.C.Terwilliger (2009).
Recent developments in phasing and structure refinement for macromolecular crystallography.
  Curr Opin Struct Biol, 19, 566-572.  
  19255472 R.M.Leal, S.C.Teixeira, M.P.Blakeley, E.P.Mitchell, and V.T.Forsyth (2009).
A preliminary neutron crystallographic study of an A-DNA crystal.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 232-235.  
  19407386 S.Z.Fisher, A.Y.Kovalevsky, J.F.Domsic, M.Mustyakimov, D.N.Silverman, R.McKenna, and P.Langan (2009).
Preliminary joint neutron and X-ray crystallographic study of human carbonic anhydrase II.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 495-498.  
  19255494 W.R.Novak, A.G.Moulin, M.P.Blakeley, I.Schlichting, G.A.Petsko, and D.Ringe (2009).
A preliminary neutron diffraction study of gamma-chymotrypsin.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 317-320.  
18566512 B.C.Bennett, A.S.Gardberg, M.D.Blair, and C.G.Dealwis (2008).
On the determinants of amide backbone exchange in proteins: a neutron crystallographic comparative study.
  Acta Crystallogr D Biol Crystallogr, 64, 764-783.  
18479128 L.Coates, H.F.Tuan, S.Tomanicek, A.Kovalevsky, M.Mustyakimov, P.Erskine, and J.Cooper (2008).
The catalytic mechanism of an aspartic proteinase explored with neutron and X-ray diffraction.
  J Am Chem Soc, 130, 7235-7237.
PDB codes: 2jji 2jjj 2vs2
  18453706 S.C.Teixeira, M.P.Blakeley, R.M.Leal, E.P.Mitchell, and V.T.Forsyth (2008).
A preliminary neutron crystallographic study of thaumatin.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 378-381.  
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.