Sandbox Reserved 772: Difference between revisions
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==Histidinol Dehydrogenase== | ==Histidinol Dehydrogenase== | ||
Histidinol dehydrogenase (HDH) is an enzyme that catalyzes the last step in the histidine biosynthetic pathway, which converts L-histidinol to L-histidine with a L-histidinaldehyde intermediate. This primordial pathway was found in bacteria, archaebacteria, fungi, and plants. HDH has been one of the most studied enzyme biochemically and genetically throughout time.<ref name="pnas"> | Histidinol dehydrogenase (HDH) is an enzyme that catalyzes the last step in the histidine biosynthetic pathway, which converts L-histidinol to L-histidine with a L-histidinaldehyde intermediate. This primordial pathway was found in bacteria, archaebacteria, fungi, and plants. HDH has been one of the most studied enzyme biochemically and genetically throughout time.<ref name="pnas">PNAS 2002 99 (4) 1859-1864; published ahead of print February 12, 2002, doi:10.1073/pnas.022476199</ref> | ||
HDH is encoded by the structural gene ''hisD'' in Brucellosis, commonly known as Maltafeve. Brucellosis is a bacterial disease transmitted by having contact with infected animals. HDH being encoded by ''hisD'' is essential for intramacrophagic replication because it provides a novel target for the development of anti-Brucella agent.<ref name="article5">http://aac.asm.org/content/51/10/3752.full.pdf+html</ref> Because HDH is absent from mammals, it has become an attractive target for inhibition as part of the herbicide development.<ref name="pnas"> | HDH is encoded by the structural gene ''hisD'' in Brucellosis, commonly known as Maltafeve. Brucellosis is a bacterial disease transmitted by having contact with infected animals. HDH being encoded by ''hisD'' is essential for intramacrophagic replication because it provides a novel target for the development of anti-Brucella agent.<ref name="article5">http://aac.asm.org/content/51/10/3752.full.pdf+html</ref> Because HDH is absent from mammals, it has become an attractive target for inhibition as part of the herbicide development.<ref name="pnas">PNAS 2002 99 (4) 1859-1864; published ahead of print February 12, 2002, doi:10.1073/pnas.022476199</ref> | ||
__TOC__ | __TOC__ | ||
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==Structure== | ==Structure== | ||
The crystal structure of histidinol dehydrogenase can be determined by x-ray crystallography. The overall structure is 48% helical (20 helices; 211 residues) and 16% beta sheet (15 strands; 73 residues).<ref name="structure">http://www.rcsb.org/pdb/explore/remediatedSequence.do?structureId=1K75&bionumber=1</ref> | The crystal structure of histidinol dehydrogenase can be determined by x-ray crystallography. The overall structure is 48% helical (20 helices; 211 residues) and 16% beta sheet (15 strands; 73 residues).<ref name="structure">http://www.rcsb.org/pdb/explore/remediatedSequence.do?structureId=1K75&bionumber=1</ref> | ||
HDH functions as a homodimer, but it consists of two monomers. The presence of Zn2+ cation is required per monomer. Each HDH monomer is made of four domains, two larger domains and two smaller domains. The two larger domains make up the globule and the two smaller domains make up the extending tail. The intertwined dimer is thought to result from domain swapping. The two domains presents a similar incomplete Rossmann fold, which 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 <ref name="pnas"> | HDH functions as a homodimer, but it consists of two monomers. The presence of Zn2+ cation is required per monomer. Each HDH monomer is made of four domains, two larger domains and two smaller domains. The two larger domains make up the globule and the two smaller domains make up the extending tail. The intertwined dimer is thought to result from domain swapping. The two domains presents a similar incomplete Rossmann fold, which 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 <ref name="pnas">PNAS 2002 99 (4) 1859-1864; published ahead of print February 12, 2002, doi:10.1073/pnas.022476199</ref> | ||
'''Related Structures''': [http://proteopedia.org/wiki/index.php/1kae 1KAE] and [http://proteopedia.org/wiki/index.php/1kar 1KAR] | '''Related Structures''': [http://proteopedia.org/wiki/index.php/1kae 1KAE] and [http://proteopedia.org/wiki/index.php/1kar 1KAR] | ||
[[Image:Monomer.gif |300px]]<ref name="pnas"> | [[Image:Monomer.gif |300px]]<ref name="pnas">PNAS 2002 99 (4) 1859-1864; published ahead of print February 12, 2002, doi:10.1073/pnas.022476199</ref> | ||
'''Figure 1.''' ''(A) Stereo view of the monomer. Domains: 1, blue; 2, green; 3, orange; 4, magenta. L-histidinol, NAD, and the Zn2� are shown as ball-and-sticks. ( B) Domain 1. Rossmann fold shown in blue, V-shaped pairs of helices (residues 25 –103) connected by a linker that forms the sixth strand are in cyan. (C) Domain 2. Rossmann fold (green) in similar orientation as B. Strand-helix hairpin completes the �-sheet (residues 1–24, magenta). (D) Topology diagram. Secondary structure elements are numbered consecutively. The chain meanders between domains in the order 2 –1-3–1-2–1-3– 4. (E) HisD dimer with one molecule colored as in A and the other shown in pale colors. Zn2� atoms and NAD bound to each monomer (red) define the position of the active site.'' | '''Figure 1.''' ''(A) Stereo view of the monomer. Domains: 1, blue; 2, green; 3, orange; 4, magenta. L-histidinol, NAD, and the Zn2� are shown as ball-and-sticks. ( B) Domain 1. Rossmann fold shown in blue, V-shaped pairs of helices (residues 25 –103) connected by a linker that forms the sixth strand are in cyan. (C) Domain 2. Rossmann fold (green) in similar orientation as B. Strand-helix hairpin completes the �-sheet (residues 1–24, magenta). (D) Topology diagram. Secondary structure elements are numbered consecutively. The chain meanders between domains in the order 2 –1-3–1-2–1-3– 4. (E) HisD dimer with one molecule colored as in A and the other shown in pale colors. Zn2� atoms and NAD bound to each monomer (red) define the position of the active site.'' | ||
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-Concurrently, His-327 (B3) donates its proton to the aldehyde oxygen | -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"> | -Repeat step 1 and then it leads to the formation of L-histidine <ref name="pnas">PNAS 2002 99 (4) 1859-1864; published ahead of print February 12, 2002, doi:10.1073/pnas.022476199</ref> | ||
==Implications or Possible Applications== | ==Implications or Possible Applications== | ||
