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Aminooxy analog of histamine is an efficient inhibitor of mammalian l-histidine decarboxylase: combined in silico and experimental evidence

Castro-Oropeza, R.; Pino-Angeles, A.; Khomutov, M. A.; Urdiales, J. L.; Moya-Garcia, A. A.; Vepsalainen, J.; Persson, Lo LU ; Sarabia, F.; Khomutov, A. and Sanchez-Jimenez, F. (2014) In Amino Acids 46(3). p.621-631
Abstract
Histamine plays highlighted roles in the development of many common, emergent and rare diseases. In mammals, histamine is formed by decarboxylation of l-histidine, which is catalyzed by pyridoxal-5'-phosphate (PLP) dependent histidine decarboxylase (HDC, EC 4.1.1.22). The limited availability and stability of the protein have delayed the characterization of its structure-function relationships. Our previous knowledge on mammalian HDC, derived from both in silico and experimental approaches, indicates that an effective competitive inhibitor should be capable to form an "external aldimine-like structure" and have an imidazole group, or its proper mimetic, which provides additional affinity of PLP-inhibitor adduct to the HDC active center.... (More)
Histamine plays highlighted roles in the development of many common, emergent and rare diseases. In mammals, histamine is formed by decarboxylation of l-histidine, which is catalyzed by pyridoxal-5'-phosphate (PLP) dependent histidine decarboxylase (HDC, EC 4.1.1.22). The limited availability and stability of the protein have delayed the characterization of its structure-function relationships. Our previous knowledge on mammalian HDC, derived from both in silico and experimental approaches, indicates that an effective competitive inhibitor should be capable to form an "external aldimine-like structure" and have an imidazole group, or its proper mimetic, which provides additional affinity of PLP-inhibitor adduct to the HDC active center. This is confirmed using HEK-293 cells transfected to express human HDC and the aminooxy analog of histidine, 4(5)-aminooxymethylimidazole (O-IMHA, IC50 a parts per thousand 2 x 10(-7) M) capable to form a PLP-inhibitor complex (oxime) in the enzyme active center. Taking advantage of the availability of the human HDC X-ray structure, we have also determined the potential interactions that could stabilize this oxime in the active site of mammalian HDC. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Histidine decarboxylase, Substrate analogs, Histamine, Drug discovery
in
Amino Acids
volume
46
issue
3
pages
621 - 631
publisher
Springer
external identifiers
  • wos:000331958900014
  • scopus:84896289072
ISSN
0939-4451
DOI
10.1007/s00726-013-1589-7
language
English
LU publication?
yes
id
0fef6cac-5f2d-4eff-a862-a96e8093d4c3 (old id 4417594)
date added to LUP
2014-05-05 07:20:53
date last changed
2017-10-22 03:00:54
@article{0fef6cac-5f2d-4eff-a862-a96e8093d4c3,
  abstract     = {Histamine plays highlighted roles in the development of many common, emergent and rare diseases. In mammals, histamine is formed by decarboxylation of l-histidine, which is catalyzed by pyridoxal-5'-phosphate (PLP) dependent histidine decarboxylase (HDC, EC 4.1.1.22). The limited availability and stability of the protein have delayed the characterization of its structure-function relationships. Our previous knowledge on mammalian HDC, derived from both in silico and experimental approaches, indicates that an effective competitive inhibitor should be capable to form an "external aldimine-like structure" and have an imidazole group, or its proper mimetic, which provides additional affinity of PLP-inhibitor adduct to the HDC active center. This is confirmed using HEK-293 cells transfected to express human HDC and the aminooxy analog of histidine, 4(5)-aminooxymethylimidazole (O-IMHA, IC50 a parts per thousand 2 x 10(-7) M) capable to form a PLP-inhibitor complex (oxime) in the enzyme active center. Taking advantage of the availability of the human HDC X-ray structure, we have also determined the potential interactions that could stabilize this oxime in the active site of mammalian HDC.},
  author       = {Castro-Oropeza, R. and Pino-Angeles, A. and Khomutov, M. A. and Urdiales, J. L. and Moya-Garcia, A. A. and Vepsalainen, J. and Persson, Lo and Sarabia, F. and Khomutov, A. and Sanchez-Jimenez, F.},
  issn         = {0939-4451},
  keyword      = {Histidine decarboxylase,Substrate analogs,Histamine,Drug discovery},
  language     = {eng},
  number       = {3},
  pages        = {621--631},
  publisher    = {Springer},
  series       = {Amino Acids},
  title        = {Aminooxy analog of histamine is an efficient inhibitor of mammalian l-histidine decarboxylase: combined in silico and experimental evidence},
  url          = {http://dx.doi.org/10.1007/s00726-013-1589-7},
  volume       = {46},
  year         = {2014},
}