Summary

Homoserine dehydrogenase, NAD binding domain

This domain adopts a Rossmann NAD binding fold. The C-terminal domain of homoserine dehydrogenase contributes a single helix to this structural domain, which is not included in the Pfam model.

InterPro entry IPR005106

Bacteria, plants and fungi metabolise aspartic acid to produce four amino acids - lysine, threonine, methionine and isoleucine - in a series of reactions known as the aspartate pathway. Additionally, several important metabolic intermediates are produced by these reactions, such as diaminopimelic acid, an essential component of bacterial cell wall biosynthesis, and dipicolinic acid, which is involved in sporulation in Gram-positive bacteria. Members of the animal kingdom do not posses this pathway and must therefore acquire these essential amino acids through their diet. Research into improving the metabolic flux through this pathway has the potential to increase the yield of the essential amino acids in important crops, thus improving their nutritional value. Additionally, since the enzymes are not present in animals, inhibitors of them are promising targets for the development of novel antibiotics and herbicides. For more information see PUBMED:11352712.

Homoserine dehydrogenase () catalyses the third step in the aspartate pathway; theNAD(P)-dependent reduction of aspartate beta-semialdehyde into homoserine PUBMED:8500624, PUBMED:8395899. Homoserine is an intermediate in the biosynthesis of threonine, isoleucine, and methionine. The enzyme can be found in a monofunctional form, in some bacteria and yeast, or a bifunctional form consisting of an N-terminal aspartokinase domain and a C-terminal homoserine dehydrogenase domain, as found in bacteria such as Escherichia coli and in plants. Structural analysis of the yeast monofunctional enzyme () indicates that the enzyme is a dimer composed of three distinct regions; an N-terminal nucleotide-binding domain, a short central dimerisation region, and a C-terminal catalytic domain PUBMED:10700284. The N-terminal domain forms a modified Rossman fold, while the catalytic domain forms a novel alpha-beta mixed sheet.

This entry represents the NAD(P)-binding domain of aspartate and homoserine dehydrogenase. Asparate dehydrogenase () is strictly specific for L-aspartate as substrate and catalyses the first step in NAD biosynthesis from aspartate. The enzyme has a higher affinity for NAD+ than NADP+ PUBMED:12496312.

Note that the C-terminus of the protein contributes a helix to this domain that is not covered by this model.

Clan

This family is a member of clan NADP_Rossmann (CL0063), which contains the following 148 members:

2-Hacid_dh_C 3Beta_HSD 3HCDH_N adh_short ADH_zinc_N AdoHcyase_NAD AdoMet_MTase AlaDh_PNT_C Amino_oxidase ApbA Bac_GDH Bin3 CheR CMAS CmcI CoA_binding Cons_hypoth95 DAO DapB_N DFP DNA_circ_N DNA_methylase DOT1 DREV DUF1442 DUF166 DUF1776 DUF185 DUF2431 DUF248 DUF268 DUF3321 DUF43 DUF519 DUF548 DUF574 DUF633 DUF752 DUF938 DXP_redisom_C DXP_reductoisom Eco57I ELFV_dehydrog Eno-Rase_FAD_bd Eno-Rase_NADH_b Enoyl_reductase Epimerase F420_oxidored FAD_binding_2 FAD_binding_3 Fibrillarin FMO-like FmrO FtsJ G6PD_N GCD14 GDI GFO_IDH_MocA GIDA GidB GLF Glyco_hydro_4 GMC_oxred_N Gp_dh_N GRDA HI0933_like HIM1 Hydrolase_5 Hydroxy-O-Methy IlvN KR LCM Ldh_1_N Lycopene_cycl Malic_M Mannitol_dh Met_10 Methyltrans_SAM Methyltransf_10 Methyltransf_11 Methyltransf_12 Methyltransf_15 Methyltransf_16 Methyltransf_2 Methyltransf_3 Methyltransf_4 Methyltransf_5 Methyltransf_8 Methyltransf_9 MethyltransfD12 MetW Mg-por_mtran_C Mqo MT-A70 MTS Mur_ligase N2227 N6-adenineMlase N6_Mtase N6_N4_Mtase NAD_binding_2 NAD_binding_3 NAD_binding_4 NAD_binding_5 NAD_Gly3P_dh_N NAS NmrA NNMT_PNMT_TEMT NodS Nol1_Nop2_Fmu NSP13 OCD_Mu_crystall PARP_regulatory PCMT PDH Polysacc_synt_2 Pox_MCEL Prenylcys_lyase PrmA PRMT5 Pyr_redox Pyr_redox_2 RmlD_sub_bind Rossmann-like rRNA_methylase RrnaAD Rsm22 Saccharop_dh SE Semialdhyde_dh Shikimate_DH Spermine_synth Strep_67kDa_ant TehB THF_DHG_CYH_C Thi4 ThiF TPMT TrkA_N TRM TRM13 tRNA_U5-meth_tr Trp_halogenase Ubie_methyltran UDPG_MGDP_dh_N UPF0020 UPF0146 V_cholerae_RfbT

Gene Ontology

Molecular function	NADP or NADPH binding (GO:0050661)
	oxidoreductase activity (GO:0016491)

External database links

PANDIT:	PF03447
PROSITE:	PDOC00800
SCOP:	1ebu
SYSTERS:	NAD_binding_3

Domain organisation

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

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Alignments

There are various ways to view or download the sequence alignments that we store. You can use a sequence viewer to look at either the seed or full alignment for the family, or you can look at a plain text version of the sequence in a variety of different formats. More...

View options

Alignment:	Seed (30) Full (2227) NCBI (4929) Metagenomics (2590)
Viewer:

Formatting options

Alignment:	Seed (30) Full (2227)
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

Very large alignments can often cause problems for the formatting tool above. If you find that downloading or viewing a large alignment is problematic, you can also download a gzip-compressed, Stockholm-format file containing the seed or full alignment for this family.

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

The main seed and full alignments are generated using sequences from the UniProt sequence database. However, we also generate alignments using sequences from the NCBI sequence database and the "metaseq" metagenomics dataset.

You can view alignments from these two additional datasets using the form above, or you can download alignments of NCBI or metagenomics sequences, as gzip-compressed files.

Pfam alignments:	Seed (30) Full (2227) NCBI (4929) Metagenomics (2590)
Full length sequences	Full-sequences (2227)

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 HMMER2.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family. 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 or full alignments.

Note: You can also download the data files for the seed, full, NCBI or metagenomics trees.

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.

Curation

Seed source:

Pfam-B_459 (release 2.1)

Previous IDs:

none

Type:

Domain

Author:

Griffiths-Jones SR

Number in seed:

30

Number in full:

2227

Average length of the domain:

124.30 aa

Average identity of full alignment:

24 %

Average coverage of the sequence by the domain:

24.66 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 9421015 -E 1000 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	21.0	21.0
Trusted cut-off	21.0	21.0
Noise cut-off	20.9	20.9

Model length:

117

Family (HMM) version:

9

Download:

download the raw HMM for this family

Species distribution

Tree controls

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The tree shows the occurrence of this domain across different species. More...

Species trees

We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.

Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.

If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.

Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.

Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.

We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.

You can use the tree controls to manipulate how the interactive tree is displayed:

show/hide the summary boxes
highlight species that are represented in the seed alignment
expand/collapse the tree or expand it to a given depth
select a sub-tree or a set of species within the tree and view them graphically or as an alignment
save a plain text representation of the tree

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Interactions

There are 3 interactions for this family. More...

NAD_binding_3 Homoserine_dh DUF108

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 MSD 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 NAD_binding_3 domain has been found.

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Family: NAD_binding_3 (PF03447)

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