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PDBsum entry 3chp
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protein ligands metals links
Hydrolase PDB id
3chp

 

 

 

 

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Contents
Protein chain
608 a.a. *
Ligands
ACT
IMD
4BO
Metals
_ZN
_YB
Waters ×236
* Residue conservation analysis
PDB id:
3chp
Name: Hydrolase
Title: Crystal structure of leukotriene a4 hydrolase in complex with (3s)-3- amino-4-oxo-4-[(4-phenylmethoxyphenyl)amino]butanoic acid
Structure: Leukotriene a-4 hydrolase. Chain: a. Synonym: lta-4 hydrolase, leukotriene a(4) hydrolase. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: lta4h, lta4. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.10Å     R-factor:   0.232     R-free:   0.278
Authors: M.M.G.M.Thunnissen,M.Adler,M.Whitlow
Key ref: T.A.Kirkland et al. (2008). Synthesis of glutamic acid analogs as potent inhibitors of leukotriene A4 hydrolase. Bioorg Med Chem Lett, 16, 4963-4983. PubMed id: 18394906 DOI: 10.1016/j.bmc.2008.03.042
Date:
10-Mar-08     Release date:   22-Apr-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P09960  (LKHA4_HUMAN) -  Leukotriene A-4 hydrolase from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		611 a.a.
608 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 2: E.C.3.3.2.6  - leukotriene-A4 hydrolase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: leukotriene A4 + H2O = leukotriene B4
leukotriene A4
 + H2O
 = leukotriene B4
      Cofactor: Zn(2+)
   Enzyme class 3: E.C.3.4.11.4  - tripeptide aminopeptidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Release of a N-terminal residue from a tripeptide.
      Cofactor: Zn(2+)
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

 

 
    Added reference    
 
 
DOI no: 10.1016/j.bmc.2008.03.042 Bioorg Med Chem Lett 16:4963-4983 (2008)
PubMed id: 18394906  
 
 
Synthesis of glutamic acid analogs as potent inhibitors of leukotriene A4 hydrolase.
T.A.Kirkland, M.Adler, J.G.Bauman, M.Chen, J.Z.Haeggström, B.King, M.J.Kochanny, A.M.Liang, L.Mendoza, G.B.Phillips, M.Thunnissen, L.Trinh, M.Whitlow, B.Ye, H.Ye, J.Parkinson, W.J.Guilford.
 
  ABSTRACT  
 
Leukotriene B(4) (LTB(4)) is a potent pro-inflammatory mediator that has been implicated in the pathogenesis of multiple diseases, including psoriasis, inflammatory bowel disease, multiple sclerosis and asthma. As a method to decrease the level of LTB(4) and possibly identify novel treatments, inhibitors of the LTB(4) biosynthetic enzyme, leukotriene A(4) hydrolase (LTA(4)-h), have been explored. Here we describe the discovery of a potent inhibitor of LTA(4)-h, arylamide of glutamic acid 4f, starting from the corresponding glycinamide 2. Analogs of 4f are then described, focusing on compounds that are both active and stable in whole blood. This effort culminated in the identification of amino alcohol 12a and amino ester 6b which meet these criteria.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21377770 S.Thangapandian, S.John, S.Sakkiah, and K.W.Lee (2011).
Pharmacophore-based virtual screening and Bayesian model for the identification of potential human leukotriene A4 hydrolase inhibitors.
  Eur J Med Chem, 46, 1593-1603.  
20298145 A.Mirshafiey, and F.Jadidi-Niaragh (2010).
Immunopharmacological role of the leukotriene receptor antagonists and inhibitors of leukotrienes generating enzymes in multiple sclerosis.
  Immunopharmacol Immunotoxicol, 32, 219-227.  
19618939 D.R.Davies, B.Mamat, O.T.Magnusson, J.Christensen, M.H.Haraldsson, R.Mishra, B.Pease, E.Hansen, J.Singh, D.Zembower, H.Kim, A.S.Kiselyov, A.B.Burgin, M.E.Gurney, and L.J.Stewart (2009).
Discovery of leukotriene A4 hydrolase inhibitors using metabolomics biased fragment crystallography.
  J Med Chem, 52, 4694-4715.
PDB codes: 3fts 3ftu 3ftv 3ftw 3ftx 3fty 3fu0 3fu3 3fu5 3fu6 3fud 3fue 3fuf 3fuh 3fui 3fuj 3fuk 3fum 3fun
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.

 

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