Aminooxy analog of histamine is an efficient inhibitor of mammalian l-histidine decarboxylase: combined in silico and experimental evidence
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4417594
- author
- 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.
- organization
- publishing date
- 2014
- 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
- pmid:24129980
- 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
- 2016-04-01 09:50:08
- date last changed
- 2022-02-17 03:44:15
@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}},
keywords = {{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}},
doi = {{10.1007/s00726-013-1589-7}},
volume = {{46}},
year = {{2014}},
}