1kae
From Proteopedia
(New page: 200px<br /><applet load="1kae" size="450" color="white" frame="true" align="right" spinBox="true" caption="1kae, resolution 1.70Å" /> '''L-HISTIDINOL DEHYDRO...) |
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| - | [[Image:1kae.gif|left|200px]]<br /><applet load="1kae" size=" | + | [[Image:1kae.gif|left|200px]]<br /><applet load="1kae" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1kae, resolution 1.70Å" /> | caption="1kae, resolution 1.70Å" /> | ||
'''L-HISTIDINOL DEHYDROGENASE (HISD) STRUCTURE COMPLEXED WITH L-HISTIDINOL (SUBSTRATE), ZINC AND NAD (COFACTOR)'''<br /> | '''L-HISTIDINOL DEHYDROGENASE (HISD) STRUCTURE COMPLEXED WITH L-HISTIDINOL (SUBSTRATE), ZINC AND NAD (COFACTOR)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The histidine biosynthetic pathway is an ancient one found in bacteria, archaebacteria, fungi, and plants that converts 5-phosphoribosyl | + | The histidine biosynthetic pathway is an ancient one found in bacteria, archaebacteria, fungi, and plants that converts 5-phosphoribosyl 1-pyrophosphate to l-histidine in 10 enzymatic reactions. This pathway provided a paradigm for the operon, transcriptional regulation of gene expression, and feedback inhibition of a pathway. l-histidinol dehydrogenase (HisD, EC ) catalyzes the last two steps in the biosynthesis of l-histidine: sequential NAD-dependent oxidations of l-histidinol to l-histidinaldehyde and then to l-histidine. HisD functions as a homodimer and requires the presence of one Zn(2+) cation per monomer. We have determined the three-dimensional structure of Escherichia coli HisD in the apo state as well as complexes with substrate, Zn(2+), and NAD(+) (best resolution is 1.7 A). Each monomer is made of four domains, 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. Zn(2+) plays a crucial role in substrate binding but is not directly involved in catalysis. The active site residue His-327 participates in acid-base catalysis, whereas Glu-326 activates a water molecule. NAD(+) binds weakly to one of the Rossmann fold domains in a manner different from that previously observed for other proteins having a Rossmann fold. |
==About this Structure== | ==About this Structure== | ||
| - | 1KAE is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with SO4, ZN, DTT, IMD, HSO, NAD and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Histidinol_dehydrogenase Histidinol dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.23 1.1.1.23] Full crystallographic information is available from [http:// | + | 1KAE is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=DTT:'>DTT</scene>, <scene name='pdbligand=IMD:'>IMD</scene>, <scene name='pdbligand=HSO:'>HSO</scene>, <scene name='pdbligand=NAD:'>NAD</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Histidinol_dehydrogenase Histidinol dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.23 1.1.1.23] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KAE OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Histidinol dehydrogenase]] | [[Category: Histidinol dehydrogenase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Barbosa, J | + | [[Category: Barbosa, J A.R G.]] |
[[Category: Cygler, M.]] | [[Category: Cygler, M.]] | ||
[[Category: Larocque, R.]] | [[Category: Larocque, R.]] | ||
[[Category: Li, Y.]] | [[Category: Li, Y.]] | ||
[[Category: Matte, A.]] | [[Category: Matte, A.]] | ||
| - | [[Category: Schrag, J | + | [[Category: Schrag, J D.]] |
[[Category: Sivaraman, J.]] | [[Category: Sivaraman, J.]] | ||
[[Category: DTT]] | [[Category: DTT]] | ||
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[[Category: zinc]] | [[Category: zinc]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:31:57 2008'' |
Revision as of 11:31, 21 February 2008
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L-HISTIDINOL DEHYDROGENASE (HISD) STRUCTURE COMPLEXED WITH L-HISTIDINOL (SUBSTRATE), ZINC AND NAD (COFACTOR)
Overview
The histidine biosynthetic pathway is an ancient one found in bacteria, archaebacteria, fungi, and plants that converts 5-phosphoribosyl 1-pyrophosphate to l-histidine in 10 enzymatic reactions. This pathway provided a paradigm for the operon, transcriptional regulation of gene expression, and feedback inhibition of a pathway. l-histidinol dehydrogenase (HisD, EC ) catalyzes the last two steps in the biosynthesis of l-histidine: sequential NAD-dependent oxidations of l-histidinol to l-histidinaldehyde and then to l-histidine. HisD functions as a homodimer and requires the presence of one Zn(2+) cation per monomer. We have determined the three-dimensional structure of Escherichia coli HisD in the apo state as well as complexes with substrate, Zn(2+), and NAD(+) (best resolution is 1.7 A). Each monomer is made of four domains, 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. Zn(2+) plays a crucial role in substrate binding but is not directly involved in catalysis. The active site residue His-327 participates in acid-base catalysis, whereas Glu-326 activates a water molecule. NAD(+) binds weakly to one of the Rossmann fold domains in a manner different from that previously observed for other proteins having a Rossmann fold.
About this Structure
1KAE is a Single protein structure of sequence from Escherichia coli with , , , , , and as ligands. Active as Histidinol dehydrogenase, with EC number 1.1.1.23 Full crystallographic information is available from OCA.
Reference
Mechanism of action and NAD+-binding mode revealed by the crystal structure of L-histidinol dehydrogenase., Barbosa JA, Sivaraman J, Li Y, Larocque R, Matte A, Schrag JD, Cygler M, Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):1859-64. Epub 2002 Feb 12. PMID:11842181
Page seeded by OCA on Thu Feb 21 13:31:57 2008
Categories: Escherichia coli | Histidinol dehydrogenase | Single protein | Barbosa, J A.R G. | Cygler, M. | Larocque, R. | Li, Y. | Matte, A. | Schrag, J D. | Sivaraman, J. | DTT | GOL | HSO | IMD | NAD | SO4 | ZN | 4 domains | Hisd | Homodimer | L-histidine biosynthesis | L-histidinol dehydrogenase | Nad cofactor | Rossman fold | Zinc
