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8  structures 3598  species 1  interaction 3998  sequences 14  architectures

Family: Histidinol_dh (PF00815)

Summary: Histidinol dehydrogenase

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This is the Wikipedia entry entitled "Histidinol dehydrogenase". More...

Histidinol dehydrogenase Edit Wikipedia article

histidinol dehydrogenase
Identifiers
EC number 1.1.1.23
CAS number 9028-27-7
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO
Histidinol dehydrogenase
PDB 1k75 EBI.jpg
the l-histidinol dehydrogenase (hisd) structure implicates domain swapping and gene duplication.
Identifiers
Symbol Histidinol_dh
Pfam PF00815
Pfam clan CL0099
InterPro IPR012131
PROSITE PDOC00534
SCOP 1k75
SUPERFAMILY 1k75

In enzymology, a histidinol dehydrogenase (HIS4) (HDH) (EC 1.1.1.23) is an enzyme that catalyzes the chemical reaction

L-histidinol + 2 NAD+ \rightleftharpoons L-histidine + 2 NADH + 2 H+

Thus, the two substrates of this enzyme are L-histidinol and NAD+, whereas its 3 products are L-histidine, NADH, and H+.

This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is L-histidinol:NAD+ oxidoreductase. This enzyme is also called L-histidinol dehydrogenase.

Histidinol dehydrogenase catalyzes the terminal step in the biosynthesis of histidine in bacteria, fungi, and plants, the four-electron oxidation of L-histidinol to histidine.

In 4-electron dehydrogenases, a single active site catalyses 2 separate oxidation steps: oxidation of the substrate alcohol to an intermediate aldehyde; and oxidation of the aldehyde to the product acid, in this case His.[1] The reaction proceeds via a tightly- or covalently-bound inter-mediate, and requires the presence of 2 NAD molecules.[1] By contrast with most dehydrogenases, the substrate is bound before the NAD coenzyme.[1] A Cys residue has been implicated in the catalytic mechanism of the second oxidative step.[1]

In bacteria HDH is a single chain polypeptide; in fungi it is the C-terminal domain of a multifunctional enzyme which catalyses three different steps of histidine biosynthesis; and in plants it is expressed as a nuclear encoded protein precursor which is exported to the chloroplast.[2][3][4]

Structural studies[edit]

As of late 2007, 4 structures have been solved for this class of enzymes, with PDB accession codes 1K75, 1KAE, 1KAH, and 1KAR.

References[edit]

  1. ^ a b c d Grubmeyer CT, Gray WR (August 1986). "A cysteine residue (cysteine-116) in the histidinol binding site of histidinol dehydrogenase". Biochemistry 25 (17): 4778–84. doi:10.1021/bi00365a009. PMID 3533140. 
  2. ^ Nagai A, Ward E, Beck J, Tada S, Chang JY, Scheidegger A, Ryals J (May 1991). "Structural and functional conservation of histidinol dehydrogenase between plants and microbes". Proc. Natl. Acad. Sci. U.S.A. 88 (10): 4133–7. doi:10.1073/pnas.88.10.4133. PMC 51612. PMID 2034659. 
  3. ^ Cowan-Jacob SW, Rahuel J, Nagai A, Iwasaki G, Ohta D (November 1996). "Crystallization and preliminary crystallographic analysis of cabbage histidinol dehydrogenase". Acta Crystallogr. D Biol. Crystallogr. 52 (Pt 6): 1188–90. doi:10.1107/S0907444996008396. PMID 15299582. 
  4. ^ Barbosa JA, Sivaraman J, Li Y, Larocque R, Matte A, Schrag JD, Cygler M (February 2002). "Mechanism of action and NAD+-binding mode revealed by the crystal structure of L-histidinol dehydrogenase". Proc. Natl. Acad. Sci. U.S.A. 99 (4): 1859–64. doi:10.1073/pnas.022476199. PMC 122284. PMID 11842181. 

Further reading[edit]

  • Adams E (1954). "Enzymatic synthesis of histidine from histidinol". J. Biol. Chem. 209 (2): 829–846. PMID 13192138. 
  • Adams E (1955). "L-Histidinal, a biosynthetic precursor of histidine". J. Biol. Chem. 217 (1): 325–344. PMID 13271397. 
  • Yourno J, Ino I (1968). "Purification and crystallization of histidinol dehydrogenase from Salmonella typhimurium LT-2". J. Biol. Chem. 243 (12): 3273–6. PMID 4872177. 
  • Loper JC (1968). "Histidinol dehydrogenase from Salmonella typhimurium Crystallization and composition studies". J. Biol. Chem. 243 (12): 3264–72. PMID 4872176. 

This article incorporates text from the public domain Pfam and InterPro IPR012131

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External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR012131

Histidinol dehydrogenase (HDH) catalyzes the terminal step in the biosynthesis of histidine in bacteria, fungi, and plants, the four-electron oxidation of L-histidinol to histidine.

In 4-electron dehydrogenases, a single active site catalyses 2 separate oxidation steps: oxidation of the substrate alcohol to an intermediate aldehyde; and oxidation of the aldehyde to the product acid, in this case His [PUBMED:3533140]. The reaction proceeds via a tightly- or covalently-bound inter-mediate, and requires the presence of 2 NAD molecules [PUBMED:3533140]. By contrast with most dehydrogenases, the substrate is bound before the NAD coenzyme [PUBMED:3533140]. A Cys residue has been implicated in the catalytic mechanism of the second oxidative step [PUBMED:3533140].

In bacteria HDH is a single chain polypeptide; in fungi it is the C-terminal domain of a multifunctional enzyme which catalyzes three different steps of histidine biosynthesis; and in plants it is expressed as nuclear encoded protein precursor which is exported to the chloroplast [PUBMED:2034659].

Gene Ontology

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Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan ALDH-like (CL0099), which has the following description:

The aldehyde dehydrogenases (ALDHs) are a superfamily of multimeric enzymes which catalyse the oxidation of a broad range of aldehydes into their corresponding carboxylic acids with the reduction of their cofactor, NAD(P) into NAD(P)H. The way that the NAD is bound is distinct from other NAD(P)-dependent oxidoreductases. The domain represented by this clan consists of two similar subdomains.

The clan contains the following 4 members:

Aldedh DUF1487 Histidinol_dh LuxC

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(16)
Full
(3998)
Representative proteomes NCBI
(3262)
Meta
(5057)
RP15
(350)
RP35
(717)
RP55
(947)
RP75
(1109)
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Key: ✓ available, x not generated, not available.

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  Seed
(16)
Full
(3998)
Representative proteomes NCBI
(3262)
Meta
(5057)
RP15
(350)
RP35
(717)
RP55
(947)
RP75
(1109)
Alignment:
Format:
Order:
Sequence:
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  Seed
(16)
Full
(3998)
Representative proteomes NCBI
(3262)
Meta
(5057)
RP15
(350)
RP35
(717)
RP55
(947)
RP75
(1109)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

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Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

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Seed source: Pfam-B_1358 (release 2.1)
Previous IDs: none
Type: Family
Author: Bateman A
Number in seed: 16
Number in full: 3998
Average length of the domain: 401.20 aa
Average identity of full alignment: 42 %
Average coverage of the sequence by the domain: 91.68 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 19.9 19.9
Trusted cut-off 21.4 20.8
Noise cut-off 19.0 18.8
Model length: 413
Family (HMM) version: 15
Download: download the raw HMM for this family

Species distribution

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Interactions

There is 1 interaction for this family. More...

Histidinol_dh

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Histidinol_dh domain has been found. There are 8 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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