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PDBsum entry 1ikt

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Oxidoreductase PDB id
1ikt
Jmol
Contents
Protein chain
115 a.a. *
Ligands
SO4 ×2
OXN
Waters ×126
* Residue conservation analysis
PDB id:
1ikt
Name: Oxidoreductase
Title: Liganded sterol carrier protein type 2 (scp-2) like domain of human multifunctional enzyme type 2 (mfe-2)
Structure: Estradiol 17 beta-dehydrogenase 4. Chain: a. Fragment: c-terminal domain, residues 618-736. Synonym: human multifunctional enzyme type 2, mfe-2. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: hsd17b4. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.75Å     R-factor:   0.192     R-free:   0.214
Authors: A.M.Haapalainen,D.M.F.Van Aalten,T.Glumoff
Key ref:
A.M.Haapalainen et al. (2001). Crystal structure of the liganded SCP-2-like domain of human peroxisomal multifunctional enzyme type 2 at 1.75 A resolution. J Mol Biol, 313, 1127-1138. PubMed id: 11700068 DOI: 10.1006/jmbi.2001.5084
Date:
07-May-01     Release date:   14-Nov-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P51659  (DHB4_HUMAN) -  Peroxisomal multifunctional enzyme type 2
Seq:
Struc:
 
Seq:
Struc:
736 a.a.
115 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 2: E.C.1.1.1  - Alcohol dehydrogenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction:
1. An alcohol + NAD+ = an aldehyde or ketone + NADH
2. A secondary alcohol + NAD+ = a ketone + NADH
alcohol
+ NAD(+)
= aldehyde or ketone
+ NADH
secondary alcohol
+ NAD(+)
= ketone
+ NADH
      Cofactor: Zn(2+) or Fe cation
   Enzyme class 3: E.C.4.2.1.107  - 3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholest-24-enoyl-CoA
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: (24R,25R)-3-alpha,7-alpha,12-alpha,24-tetrahydroxy-5-beta-cholestanoyl- CoA = (24E)-3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholest-24-enoyl- CoA + H2O
   Enzyme class 4: E.C.4.2.1.119  - Enoyl-CoA hydratase 2.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: (3R)-3-hydroxyacyl-CoA = (2E)-2-enoyl-CoA + H2O
(3R)-3-hydroxyacyl-CoA
= (2E)-2-enoyl-CoA
+ H(2)O
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     sterol binding     1 term  

 

 
    reference    
 
 
DOI no: 10.1006/jmbi.2001.5084 J Mol Biol 313:1127-1138 (2001)
PubMed id: 11700068  
 
 
Crystal structure of the liganded SCP-2-like domain of human peroxisomal multifunctional enzyme type 2 at 1.75 A resolution.
A.M.Haapalainen, D.M.van Aalten, G.Meriläinen, J.E.Jalonen, P.Pirilä, R.K.Wierenga, J.K.Hiltunen, T.Glumoff.
 
  ABSTRACT  
 
beta-Oxidation of amino acyl coenzyme A (acyl-CoA) species in mammalian peroxisomes can occur via either multifunctional enzyme type 1 (MFE-1) or type 2 (MFE-2), both of which catalyze the hydration of trans-2-enoyl-CoA and the dehydrogenation of 3-hydroxyacyl-CoA, but with opposite chiral specificity. MFE-2 has a modular organization of three domains. The function of the C-terminal domain of the mammalian MFE-2, which shows similarity with sterol carrier protein type 2 (SCP-2), is unclear. Here, the structure of the SCP-2-like domain comprising amino acid residues 618-736 of human MFE-2 (d Delta h Delta SCP-2L) was solved at 1.75 A resolution in complex with Triton X-100, an analog of a lipid molecule. This is the first reported structure of an MFE-2 domain. The d Delta h Delta SCP-2L has an alpha/beta-fold consisting of five beta-strands and five alpha-helices; the overall architecture resembles the rabbit and human SCP-2 structures. However, the structure of d Delta h Delta SCP-2L shows a hydrophobic tunnel that traverses the protein, which is occupied by an ordered Triton X-100 molecule. The tunnel is large enough to accommodate molecules such as straight-chain and branched-chain fatty acyl-CoAs and bile acid intermediates. Large empty apolar cavities are observed near the exit of the tunnel and between the helices C and D. In addition, the C-terminal peroxisomal targeting signal is ordered in the structure and solvent-exposed, which is not the case with unliganded rabbit SCP-2, supporting the hypothesis of a ligand-assisted targeting mechanism.
 
  Selected figure(s)  
 
Figure 4.
Figure 4. A drawing of the contact environment between the Triton X-100 molecule and dDhDSCP-2L. For clarity, the distances are shown in Table 1. Only one hydrogen bond (3.1 Å) is formed between NE2 of Gln108 and O55 of the Triton molecule. Triton X-100 consists of three structural parts: (1,1,3,3-tetramethyl)butyl, phenyl and ethoxy-repeats. The Figure was produced with ChemDraw software.
Figure 6.
Figure 6. Electrostatic surface potential of the liganded dDhDSCP-2L structure. Negative surface potentials are marked with red, positive surface potentials with blue and neutral potentials with white. (a) Exit of the tunnel, showing the tetramethylbutyl-fragment of the ligand. There exists an extra hole, marked with an arrow, near the exit of the tunnel, which is not present in the rabbit SCP-2 crystal structure.[24] (b) Entrance of the tunnel, displaying the solvent-exposed ethoxy-repeat of the ligand. The Figures were produced with Swiss-PdbViewer. [30]
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2001, 313, 1127-1138) copyright 2001.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21320074 T.J.Haataja, M.K.Koski, J.K.Hiltunen, and T.Glumoff (2011).
Peroxisomal multifunctional enzyme type 2 from the fruitfly: dehydrogenase and hydratase act as separate entities, as revealed by structure and kinetics.
  Biochem J, 435, 771-781.
PDB code: 3oml
20922486 A.K.Goroncy, K.Murayama, M.Shirouzu, S.Kuramitsu, T.Kigawa, and S.Yokoyama (2010).
NMR and X-ray structures of the putative sterol carrier protein 2 from Thermus thermophilus HB8 show conformational changes.
  J Struct Funct Genomics, 11, 247-256.  
19575662 S.Raychaudhuri, and W.A.Prinz (2010).
The diverse functions of oxysterol-binding proteins.
  Annu Rev Cell Dev Biol, 26, 157-177.  
19130179 D.H.Dyer, I.Vyazunova, J.M.Lorch, K.T.Forest, and Q.Lan (2009).
Characterization of the yellow fever mosquito sterol carrier protein-2 like 3 gene and ligand-bound protein structure.
  Mol Cell Biochem, 326, 67-77.
PDB codes: 3bkr 3bks
19204834 X.Wu, N.Liu, Y.He, and Y.Chen (2009).
Cloning, expression, and characterization of a novel diketoreductase from Acinetobacter baylyi.
  Acta Biochim Biophys Sin (Shanghai), 41, 163-170.  
18687588 B.S.Zheng, E.Rönnberg, L.Viitanen, T.A.Salminen, K.Lundgren, T.Moritz, and J.Edqvist (2008).
Arabidopsis sterol carrier protein-2 is required for normal development of seeds and seedlings.
  J Exp Bot, 59, 3485-3499.  
17485462 M.H.Ko, and L.Puglielli (2007).
The sterol carrier protein SCP-x/pro-SCP-2 gene has transcriptional activity and regulates the Alzheimer disease gamma-secretase.
  J Biol Chem, 282, 19742-19752.  
16684886 G.Hagelueken, T.M.Adams, L.Wiehlmann, U.Widow, H.Kolmar, B.Tümmler, D.W.Heinz, and W.D.Schubert (2006).
The crystal structure of SdsA1, an alkylsulfatase from Pseudomonas aeruginosa, defines a third class of sulfatases.
  Proc Natl Acad Sci U S A, 103, 7631-7636.
PDB codes: 2cfu 2cfz 2cg2 2cg3
16501878 J.Edqvist, and K.Blomqvist (2006).
Fusion and fission, the evolution of sterol carrier protein-2.
  J Mol Evol, 62, 292-306.  
17212780 L.Viitanen, M.Nylund, D.M.Eklund, C.Alm, A.K.Eriksson, J.Tuuf, T.A.Salminen, P.Mattjus, and J.Edqvist (2006).
Characterization of SCP-2 from Euphorbia lagascae reveals that a single Leu/Met exchange enhances sterol transfer activity.
  FEBS J, 273, 5641-5655.  
16385454 S.Ferdinandusse, M.S.Ylianttila, J.Gloerich, M.K.Koski, W.Oostheim, H.R.Waterham, J.K.Hiltunen, R.J.Wanders, and T.Glumoff (2006).
Mutational spectrum of D-bifunctional protein deficiency and structure-based genotype-phenotype analysis.
  Am J Hum Genet, 78, 112-124.  
15272157 A.W.Schüttelkopf, and D.M.van Aalten (2004).
PRODRG: a tool for high-throughput crystallography of protein-ligand complexes.
  Acta Crystallogr D Biol Crystallogr, 60, 1355-1363.  
15456765 J.Edqvist, E.Rönnberg, S.Rosenquist, K.Blomqvist, L.Viitanen, T.A.Salminen, M.Nylund, J.Tuuf, and P.Mattjus (2004).
Plants express a lipid transfer protein with high similarity to mammalian sterol carrier protein-2.
  J Biol Chem, 279, 53544-53553.  
12855689 D.H.Dyer, S.Lovell, J.B.Thoden, H.M.Holden, I.Rayment, and Q.Lan (2003).
The structural determination of an insect sterol carrier protein-2 with a ligand-bound C16 fatty acid at 1.35-A resolution.
  J Biol Chem, 278, 39085-39091.
PDB code: 1pz4
12543708 D.W.Russell (2003).
The enzymes, regulation, and genetics of bile acid synthesis.
  Annu Rev Biochem, 72, 137-174.  
12198300 M.B.Lascombe, M.Ponchet, P.Venard, M.L.Milat, J.P.Blein, and T.Prangé (2002).
The 1.45 A resolution structure of the cryptogein-cholesterol complex: a close-up view of a sterol carrier protein (SCP) active site.
  Acta Crystallogr D Biol Crystallogr, 58, 1442-1447.
PDB code: 1lri
12501157 R.L.Rich, and D.G.Myszka (2002).
Survey of the year 2001 commercial optical biosensor literature.
  J Mol Recognit, 15, 352-376.  
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.