1kah: Difference between revisions

Revision as of 14:31, 21 February 2008

L-HISTIDINOL DEHYDROGENASE (HISD) STRUCTURE COMPLEXED WITH L-HISTIDINE (PRODUCT), ZN AND NAD (COFACTOR)

OverviewOverview

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 StructureAbout this Structure

1KAH 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.

ReferenceReference

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

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-[[Image:1kah.gif|left|200px]]<br /><applet load="1kah" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1kah.gif|left|200px]]<br /><applet load="1kah" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1kah, resolution 2.10&Aring;" />
 '''L-HISTIDINOL DEHYDROGENASE (HISD) STRUCTURE COMPLEXED WITH L-HISTIDINE (PRODUCT), ZN AND NAD (COFACTOR)'''<br />
 ==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.
+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==
-KAH 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 ZN and HIS 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1KAH OCA].
+KAH 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=ZN:'>ZN</scene> and <scene name='pdbligand=HIS:'>HIS</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=1KAH OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Histidinol dehydrogenase]]
 [[Category: Single protein]]
-[[Category: Barbosa, J.A.R.G.]]
+[[Category: Barbosa, J A.R G.]]
 [[Category: Cygler, M.]]
 [[Category: Larocque, R.]]
 [[Category: Li, Y.]]
 [[Category: Matte, A.]]
-[[Category: Schrag, J.D.]]
+[[Category: Schrag, J D.]]
 [[Category: Sivaraman, J.]]
 [[Category: HIS]]
@@ Line 32: / Line 32: @@
 [[Category: zinc]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 19:00:07 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:31:52 2008''