Sandbox Reserved 772

This Sandbox is Reserved from Sep 25, 2013, through Mar 31, 2014 for use in the course "BCH455/555 Proteins and Molecular Mechanisms" taught by Michael B. Goshe at the North Carolina State University. This reservation includes Sandbox Reserved 299, Sandbox Reserved 300 and Sandbox Reserved 760 through Sandbox Reserved 779.

To get started: Click the edit this page tab at the top. Save the page after each step, then edit it again. Click the 3D button (when editing, above the wikitext box) to insert Jmol. show the Scene authoring tools, create a molecular scene, and save it. Copy the green link into the page. Add a description of your scene. Use the buttons above the wikitext box for bold, italics, links, headlines, etc. More help: Help:Editing

spinqualitylabelsall models INSERT CAPTION HERE Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

this is a caption

Histidinol DehydrogenaseHistidinol Dehydrogenase

Histidinol dehydrogenase (HDH) is coded by the structural gene hisD. Histidinol dehydrogenase catalyzes the last step in the histidine biosynthetic pathway. This pathway was found in bacteria, archaebacteria, fungi, and plants. The pathway involves the conversion of L-histidinol to L-histidine with a L-histidinaldehyde intermediate

General InformationGeneral Information

Gene Name: hisD

Organism: Escherichia coli (strain K12)

Classification: Oxidoreductase

Length: 434 Amino Acids

Chains: A, B

Molecular Weight: 46107.65 Da

Isoelectric Point: 5.06

StructureStructure

The overall structure is 48% helical (20 helices; 211 residues) and 16% beta sheet (15 strands; 73 residues).

HisD is a monomer, but it functions as a homodimer. The presence of Zn2+ cation is required per monomer. Each hisD monomer is made of four domains,two larger domains (globule) and two smaller domains (extending tail), whereas the intertwined dimer possibly results from domain swapping. Two domains display a very similar incomplete Rossmann fold that suggests an ancient event of gene duplication. Residues from both monomers form the active site. The active site, residue His-327, participates in acid-base catalysis

Related Structures: 1KAE and 1KAR

Enzymatic MechanismEnzymatic Mechanism

This bifunctional enzyme converts L-histidinol to L-histidine through a L-histidinaldehyde intermediate. The process is as follows: -extraction of one proton and one hydride from L-histidinol[1] -reduced NADH leaves and replaced by NAD+ -repeat the first step -His-327 abstracts a proton from the hydroxyl group, and the second NAD+ molecule is reduced by a hydride -formation of l-histidine.

Implications or Possible ApplicationsImplications or Possible Applications

Brucellosis, commonly known as Maltafever, is the most widespread bacterial zoonosis worldwide. 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.

Inhibition of its enzymatic activity with specific inhibitors will prevent intramacrophagic multiplication of Brucella. Histidinol dehydrogenase being exclusively necessary for the growth of the bacteria inside the macrophage of the host, and having no counterpart in mammalians, it constitutes a therapeutic target for the development of an anti-infectious treatment against intracellular pathogens.