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PDBsum entry 2ilt

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protein ligands metals links
Oxidoreductase PDB id
2ilt
Jmol
Contents
Protein chain
275 a.a. *
Ligands
NAP
NN1
Metals
_NI ×2
Waters ×173
* Residue conservation analysis
PDB id:
2ilt
Name: Oxidoreductase
Title: Human 11-beta-hydroxysteroid dehydrogenase (hsd1) with NADP adamantane sulfone inhibitor
Structure: Corticosteroid 11-beta-dehydrogenase isozyme 1. Chain: a. Fragment: dehydrogenase domain (residues 23-284). Synonym: 11-dh, 11-beta-hydroxysteroid dehydrogenase 1, 11- engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: hsd11b1
Resolution:
2.30Å     R-factor:   0.212     R-free:   0.275
Authors: K.L.Longenecker,B.Sorensen,R.Judge,W.Qin,J.T.Link
Key ref: B.Sorensen et al. (2007). Adamantane sulfone and sulfonamide 11-beta-HSD1 Inhibitors. Bioorg Med Chem Lett, 17, 527-532. PubMed id: 17070044 DOI: 10.1016/j.bmcl.2006.10.008
Date:
03-Oct-06     Release date:   03-Apr-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P28845  (DHI1_HUMAN) -  Corticosteroid 11-beta-dehydrogenase isozyme 1
Seq:
Struc:
292 a.a.
275 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 14 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.1.1.1.146  - 11-beta-hydroxysteroid dehydrogenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: An 11-beta-hydroxysteroid + NADP+ = an 11-oxosteroid + NADPH
11-beta-hydroxysteroid
+
NADP(+)
Bound ligand (Het Group name = NAP)
corresponds exactly
= 11-oxosteroid
+ NADPH
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   4 terms 
  Biological process     metabolic process   7 terms 
  Biochemical function     oxidoreductase activity     3 terms  

 

 
    Added reference    
 
 
DOI no: 10.1016/j.bmcl.2006.10.008 Bioorg Med Chem Lett 17:527-532 (2007)
PubMed id: 17070044  
 
 
Adamantane sulfone and sulfonamide 11-beta-HSD1 Inhibitors.
B.Sorensen, M.Winn, J.Rohde, Q.Shuai, J.Wang, S.Fung, K.Monzon, W.Chiou, D.Stolarik, H.Imade, L.Pan, X.Deng, L.Chovan, K.Longenecker, R.Judge, W.Qin, M.Brune, H.Camp, E.U.Frevert, P.Jacobson, J.T.Link.
 
  ABSTRACT  
 
Potent and selective adamantane sulfone and sulfonamide inhibitors of 11-beta-HSD-1 have been discovered. Selected compounds from these series have robust pharmacokinetic profiles and strongly inhibit liver, fat, and brain HSD1 for extended periods after oral dosing.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21354674 J.Liu, D.Obando, V.Liao, T.Lifa, and R.Codd (2011).
The many faces of the adamantyl group in drug design.
  Eur J Med Chem, 46, 1949-1963.  
20872873 M.Actis, M.C.Connelly, A.Mayasundari, C.Punchihewa, and N.Fujii (2011).
A structure-activity relationship study of small-molecule inhibitors of GLI1-mediated transcription.
  Biopolymers, 95, 24-30.  
18069989 C.Hale, M.Véniant, Z.Wang, M.Chen, J.McCormick, R.Cupples, D.Hickman, X.Min, A.Sudom, H.Xu, G.Matsumoto, C.Fotsch, D.J.St Jean, and M.Wang (2008).
Structural characterization and pharmacodynamic effects of an orally active 11beta-hydroxysteroid dehydrogenase type 1 inhibitor.
  Chem Biol Drug Des, 71, 36-44.
PDB code: 3bzu
18363514 K.A.Hughes, S.P.Webster, and B.R.Walker (2008).
11-Beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitors in type 2 diabetes mellitus and obesity.
  Expert Opin Investig Drugs, 17, 481-496.  
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.