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9  structures 3616  species 1  interaction 3787  sequences 15  architectures

Family: Porphobil_deamC (PF03900)

Summary: Porphobilinogen deaminase, C-terminal domain

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Porphobilinogen deaminase, C-terminal domain Provide feedback

No Pfam abstract.

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR022418

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 C-terminal domain of porphobilinogen deaminase, an enzyme involved in tetrapyrrole biosynthesis. The structure of this alpha/beta domain consists of alpha-beta(3)-alpha in two layers [PUBMED:1522882]. 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

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Domain organisation

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Alignments

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  Seed
(21)
Full
(3787)
Representative proteomes NCBI
(2829)
Meta
(1539)
RP15
(334)
RP35
(692)
RP55
(920)
RP75
(1082)
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Format an alignment

  Seed
(21)
Full
(3787)
Representative proteomes NCBI
(2829)
Meta
(1539)
RP15
(334)
RP35
(692)
RP55
(920)
RP75
(1082)
Alignment:
Format:
Order:
Sequence:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(21)
Full
(3787)
Representative proteomes NCBI
(2829)
Meta
(1539)
RP15
(334)
RP35
(692)
RP55
(920)
RP75
(1082)
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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Curation and family details

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Seed source: SCOP
Previous IDs: none
Type: Domain
Author: Bateman A, Griffiths-Jones SR
Number in seed: 21
Number in full: 3787
Average length of the domain: 74.20 aa
Average identity of full alignment: 34 %
Average coverage of the sequence by the domain: 23.23 %

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 21.3 21.3
Trusted cut-off 21.4 21.6
Noise cut-off 21.2 21.2
Model length: 74
Family (HMM) version: 10
Download: download the raw HMM for this family

Species distribution

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Interactions

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

Porphobil_deam

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_deamC domain has been found. There are 9 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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