Sandbox Reserved 772: Difference between revisions
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This bifunctional enzyme converts L-histidinol to L-histidine through a L-histidinaldehyde intermediate. His-327 and Glu-326 are the active sites (proton acceptors) of HDH.<ref name="info">http://www.uniprot.org/uniprot/P06988#section_terms</ref> | This bifunctional enzyme converts L-histidinol to L-histidine through a L-histidinaldehyde intermediate. His-327 and Glu-326 are the active sites (proton acceptors) of HDH.<ref name="info">http://www.uniprot.org/uniprot/P06988#section_terms</ref> | ||
The reaction above is | The reaction above is as follows: | ||
-1 proton and 1 hydride are abstracted from L-histidinol by His-327 (B1). NAD+ accepts hydride. | |||
-L-histdinol becomes L-histidinaldehyde (sp2) | |||
-Reduced NADH cofactor leaves and then is replaced by another NAD+ | |||
-Water is activated by Glu-326 (B2) and makes a nucleophilic attack on the reactive carbon. | |||
-Concurrently, His-327 (B3) donates its proton to the aldehyde oxygen | |||
-Repeat step 1 and then it leads to the formation of L-histidine <ref name="pnas">http://www.pnas.org.prox.lib.ncsu.edu/content/99/4/1859.full.pdf</ref> | |||
==Implications or Possible Applications== | ==Implications or Possible Applications== | ||
Brucellosis, commonly known as Maltafever, is the most widespread bacterial zoonosis worldwide. It is a bacterial disease of human beings transmitted by contact with infected animals or infected meat or milk products. It causes fever and headaches. Its causative agent, Brucella spp., is a facultative intracellular pathogen developed inside the host’s macrophages. | Brucellosis, commonly known as Maltafever, is the most widespread bacterial zoonosis worldwide. It is a bacterial disease of human beings transmitted by contact with infected animals or infected meat or milk products. It causes fever and headaches. Its causative agent, Brucella spp., is a facultative intracellular pathogen developed inside the host’s macrophages. | ||
The absence of a vaccine for humans and the appearing resistance of Brucella spp. to anti-biotic chemotherapy points to the necessity to develop new therapeutic strategies to eradicate this reemerging pathogen. The virulome analysis of Brucella suis shows that genes involved in the biosynthesis of amino acids are essential for the virulence of the bacteria. | The absence of a vaccine for humans and the appearing resistance of Brucella spp. to anti-biotic chemotherapy points to the necessity to develop new therapeutic strategies to eradicate this reemerging pathogen. The virulome analysis of Brucella suis shows that genes involved in the biosynthesis of amino acids are essential for the virulence of the bacteria. | ||
Inhibition of its enzymatic activity with specific inhibitors will prevent intramacrophagic multiplication of Brucella. Histidinol dehydrogenase | Inhibition of its enzymatic activity with specific inhibitors will prevent intramacrophagic multiplication of Brucella. Histidinol dehydrogenase is an amino acid biosynthetic enzyme, which can provide a novel target for the development of anti-Brucella agents. Histidinol dehydrogenase has no counterpart in mammalians; therefore, it constitutes a therapeutic target for the development of an anti-infectious treatment against intracellular pathogens.<ref name="article2">http://pubs.rsc.org.prox.lib.ncsu.edu/en/content/articlepdf/2011/md/c1md00146a</ref> | ||
==References== | ==References== | ||
<references /> | <references /> | ||