Summary: Porphobilinogen deaminase, dipyromethane cofactor binding domain
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Porphobilinogen deaminase, dipyromethane cofactor binding domain Provide feedback
No Pfam abstract.
External database links
PROSITE: | PDOC00461 |
SCOP: | 1pda |
This tab holds annotation information from the InterPro database.
InterPro entry IPR022417
Tetrapyrroles are large macrocyclic compounds derived from a common biosynthetic pathway [PUBMED:16564539]. The end-product, uroporphyrinogen III, is used to synthesise a number of important molecules, including vitamin B12, haem, sirohaem, chlorophyll, coenzyme F430 and phytochromobilin [PUBMED:17227226].
- The first stage in tetrapyrrole synthesis is the synthesis of 5-aminoaevulinic acid ALA via two possible routes: (1) condensation of succinyl CoA and glycine (C4 pathway) using ALA synthase (EC), or (2) decarboxylation of glutamate (C5 pathway) via three different enzymes, glutamyl-tRNA synthetase (EC) to charge a tRNA with glutamate, glutamyl-tRNA reductase (EC) to reduce glutamyl-tRNA to glutamate-1-semialdehyde (GSA), and GSA aminotransferase (EC) to catalyse a transamination reaction to produce ALA.
- The second stage is to convert ALA to uroporphyrinogen III, the first macrocyclic tetrapyrrolic structure in the pathway. This is achieved by the action of three enzymes in one common pathway: porphobilinogen (PBG) synthase (or ALA dehydratase, EC) to condense two ALA molecules to generate porphobilinogen; hydroxymethylbilane synthase (or PBG deaminase, EC) to polymerise four PBG molecules into preuroporphyrinogen (tetrapyrrole structure); and uroporphyrinogen III synthase (EC) to link two pyrrole units together (rings A and D) to yield uroporphyrinogen III.
- Uroporphyrinogen III is the first branch point of the pathway. To synthesise cobalamin (vitamin B12), sirohaem, and coenzyme F430, uroporphyrinogen III needs to be converted into precorrin-2 by the action of uroporphyrinogen III methyltransferase (EC). To synthesise haem and chlorophyll, uroporphyrinogen III needs to be decarboxylated into coproporphyrinogen III by the action of uroporphyrinogen III decarboxylase (EC) [PUBMED:11215515].
Porphobilinogen deaminase (also known as hydroxymethylbilane synthase, EC) functions during the second stage of tetrapyrrole biosynthesis. This enzyme catalyses the polymerisation of four PBG molecules into the tetrapyrrole structure, preuroporphyrinogen, with the concomitant release of four molecules of ammonia. This enzyme uses a unique dipyrro-methane cofactor made from two molecules of PBG, which is covalently attached to a cysteine side chain. The tetrapyrrole product is synthesized in an ordered, sequential fashion, by initial attachment of the first pyrrole unit (ring A) to the cofactor, followed by subsequent additions of the remaining pyrrole units (rings B, C, D) to the growing pyrrole chain [PUBMED:11215515]. The link between the pyrrole ring and the cofactor is broken once all the pyrroles have been added. This enzyme is folded into three distinct domains that enclose a single, large active site that makes use of an aspartic acid as its one essential catalytic residue, acting as a general acid/base during catalysis [PUBMED:12555854, PUBMED:1522882]. A deficiency of hydroxymethylbilane synthase is implicated in the neuropathic disease, Acute Intermittent Porphyria (AIP) [PUBMED:16935474].
This entry represents the N-terminal domains 1 and 2 of porphobilinogen deaminase, an enzyme involved in tetrapyrrole biosynthesis. The structure of this domain consists of a duplication of two similar intertwined domains with three layers of (a/b/a) each. Porphobilinogen deaminase has a three-domain structure. Domains 1 (N-terminal) and 2 are duplications with the same structure, resembling the transferrins and periplasmic binding proteins. The dipyrromethane cofactor is covalently linked to domain 3 (C-terminal), but is bound by extensive salt-bridges and hydrogen-bonds within the cleft between domains 1 and 2, at a position corresponding to the binding sites for small-molecule ligands in the analogous proteins [PUBMED:1522882]. The enzyme has a single catalytic site, and the flexibility between domains is thought to aid elongation of the polypyrrole product in the active-site cleft of the enzyme.
Gene Ontology
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
Molecular function | hydroxymethylbilane synthase activity (GO:0004418) |
Biological process | tetrapyrrole biosynthetic process (GO:0033014) |
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 PBP (CL0177), which has the following description:
Periplasmic binding proteins (PBPs) consist of two large lobes that close around the bound ligand. This architecture is reiterated in transcriptional regulators, such as the lac repressors. In the process of evolution, genes encoding the PBPs have fused with genes for integral membrane proteins. Thus, diverse mammalian receptors contain extracellular ligand binding domains that are homologous to the PBPs; these include glutamate/glycine-gated ion channels such as the NMDA receptor, G protein-coupled receptors, including metabotropic glutamate, GABA-B, calcium sensing, and pheromone receptors, and atrial natriuretic peptide-guanylate cyclase receptors [2].
The clan contains the following 27 members:
DctP DUF3834 HisG Lig_chan-Glu_bd Lipoprotein_8 Lipoprotein_9 LysR_substrate Mycoplasma_p37 NMT1 NMT1_2 NMT1_3 OpuAC PBP_like PBP_like_2 PDT Phosphonate-bd Porphobil_deam SBP_bac_1 SBP_bac_11 SBP_bac_3 SBP_bac_5 SBP_bac_6 SBP_bac_8 TctC Transferrin VitK2_biosynth YhfZ_CAlignments
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Seed (707) |
Full (7866) |
Representative proteomes | UniProt (31183) |
NCBI (42015) |
Meta (2562) |
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RP15 (953) |
RP35 (3520) |
RP55 (7444) |
RP75 (12644) |
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PP/heatmap | 1 |
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key:
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Seed (707) |
Full (7866) |
Representative proteomes | UniProt (31183) |
NCBI (42015) |
Meta (2562) |
||||
---|---|---|---|---|---|---|---|---|---|
RP15 (953) |
RP35 (3520) |
RP55 (7444) |
RP75 (12644) |
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Raw Stockholm | |||||||||
Gzipped |
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
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Curation and family details
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Curation
Seed source: | SCOP |
Previous IDs: | none |
Type: | Domain |
Sequence Ontology: | SO:0000417 |
Author: |
Bateman A |
Number in seed: | 707 |
Number in full: | 7866 |
Average length of the domain: | 204.20 aa |
Average identity of full alignment: | 42 % |
Average coverage of the sequence by the domain: | 62.36 % |
HMM information
HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
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Model details: |
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Model length: | 208 | ||||||||||||
Family (HMM) version: | 21 | ||||||||||||
Download: | download the raw HMM for this family |
Species distribution
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Interactions
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 Porphobil_deam domain has been found. There are 20 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 sequence.
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