Summary: Delta-aminolevulinic acid dehydratase
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This is the Wikipedia entry entitled "Porphobilinogen synthase". More...
Porphobilinogen synthase Edit Wikipedia article
| porphobilinogen synthase | |||||||||
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| Identifiers | |||||||||
| EC number | 4.2.1.24 | ||||||||
| CAS number | 9036-37-7 | ||||||||
| 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 | ||||||||
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| Delta-aminolevulinic acid dehydratase | |
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| Identifiers | |
| Symbol | ALAD |
| Entrez | 210 |
| HUGO | 395 |
| OMIM | 125270 |
| RefSeq | NM_001003945 |
| UniProt | P13716 |
| Other data | |
| EC number | 4.2.1.24 |
| Locus | Chr. 9 q32 |
| ALAD | |||||||||
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| high resolution crystal structure of a mg2-dependent 5-aminolevulinic acid dehydratase | |||||||||
| Identifiers | |||||||||
| Symbol | ALAD | ||||||||
| Pfam | PF00490 | ||||||||
| Pfam clan | CL0036 | ||||||||
| InterPro | IPR001731 | ||||||||
| PROSITE | PDOC00153 | ||||||||
| SCOP | 1aw5 | ||||||||
| SUPERFAMILY | 1aw5 | ||||||||
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Porphobilinogen synthase (or ALA dehydratase, or aminolevulinate dehydratase) synthesizes porphobilinogen through the asymmetric condensation of two molecules of aminolevulinic acid. All natural tetrapyrroles, including hemes, chlorophylls and vitamin B12, share porphobilinogen as a common precursor.
It catalyzes the second step of the biosynthesis of porphyrin. The porphobilinogen synthase catalyzed reaction is the first common step in the biosynthesis of all biological tetrapyrroles.
Porphobilinogen synthase is the prototype morpheein.[1]
[edit] Deficiency
A deficiency of porphobilinogen synthase is usually acquired (rather than hereditary) and can be caused by heavy metal poisoning, especially lead poisoning, as the enzyme is very susceptible to inhibition by heavy metals.[2]
Hereditary insufficiency of porphobilinogen synthase is called porphobilinogen synthase (or ALA dehydratase) deficiency poprhyria. It is an extremely rare cause of porphyria,[3] with less than 10 cases ever reported.[4]
Heme synthesisânote that some reactions occur in the cytoplasm and some in the mitochondrion (yellow)
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Lead poisoning works on the cellular level by binding to this enzyme, rendering it useless.
[edit] References
- ^ . PMID 22037356.
- ^ ALA dehydratase reaction, from NetBiochem at the University of Utah. Last modified 1/5/95
- ^ Jaffe EK, Stith L (February 2007). "ALAD porphyria is a conformational disease". Am. J. Hum. Genet. 80 (2): 329â37. doi:10.1086/511444. PMC 1785348. PMID 17236137. Retrieved 2008-12-10.
- ^ Overview of the Porphyrias at The Porphyrias Consortium (a part of NIH Rare Diseases Clinical Research Network (RDCRN)) Retrieved June 2011
[edit] External links
- delta-Aminolevulinic Acid Dehydratase at the US National Library of Medicine Medical Subject Headings (MeSH)
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This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
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No Pfam abstract.
External database links
| HOMSTRAD: | ALAD |
| PANDIT: | PF00490 |
| PROSITE: | PDOC00153 |
| Pseudofam: | PF00490 |
| SCOP: | 1aw5 |
| SYSTERS: | ALAD |
This tab holds annotation information from the InterPro database.
InterPro entry IPR001731
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].
This entry represents porphobilinogen (PBG) synthase (PBGS, or 5-aminoaevulinic acid dehydratase, or ALAD, EC), which functions during the second stage of tetrapyrrole biosynthesis. This enzyme catalyses a Knorr-type condensation reaction between two molecules of ALA to generate porphobilinogen, the pyrrolic building block used in later steps [PUBMED:17311232]. The structure of the enzyme is based on a TIM barrel topology made up of eight identical subunits, where each subunit binds to a metal ion that is essential for activity, usually zinc (in yeast, mammals and certain bacteria) or magnesium (in plants and other bacteria). A lysine has been implicated in the catalytic mechanism [PUBMED:3092810]. The lack of PBGS enzyme causes a rare porphyric disorder known as ALAD porphyria, which appears to involve conformational changes in the enzyme [PUBMED:17236137].
Gene Ontology
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
| Molecular function | metal ion binding (GO:0046872) |
| porphobilinogen synthase activity (GO:0004655) | |
| 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 TIM_barrel (CL0036), which contains the following 57 members:
Ala_racemase_N ALAD Aldolase AP_endonuc_2 BtpA CdhD CutC DAHP_synth_1 DAHP_synth_2 DeoC DHDPS DHO_dh DHquinase_I DUF1341 DUF2090 DUF556 DUF561 DUF692 DUF993 Dus F_bP_aldolase FMN_dh G3P_antiterm Glu_syn_central Glu_synthase His_biosynth HMGL-like IGPS IMPDH iPGM_N MtrH NanE NAPRTase NeuB NMO OMPdecase Orn_Arg_deC_N Oxidored_FMN PcrB PdxJ PhosphMutase PRAI Pterin_bind QRPTase_C Racemase_4 RhaA Ribul_P_3_epim SOR_SNZ Tagatose_6_P_K ThiG TIM TIM-br_sig_trns TMP-TENI Transaldolase Trp_syntA UvdE UxuAAlignments
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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| Seed (165) |
Full (3912) |
Representative proteomes | NCBI (2899) |
Meta (2727) |
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| RP15 (362) |
RP35 (710) |
RP55 (948) |
RP75 (1117) |
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| PP/heatmap | 1 | |||||||
| Pfam viewer | ||||||||
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| Seed (165) |
Full (3912) |
Representative proteomes | NCBI (2899) |
Meta (2727) |
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| RP15 (362) |
RP35 (710) |
RP55 (948) |
RP75 (1117) |
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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.
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.
HMM logo
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Trees
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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.
Curation
| Seed source: | Prosite |
| Previous IDs: | none |
| Type: | Domain |
| Author: | Finn RD, Griffiths-Jones SR |
| Number in seed: | 165 |
| Number in full: | 3912 |
| Average length of the domain: | 314.40 aa |
| Average identity of full alignment: | 48 % |
| Average coverage of the sequence by the domain: | 95.89 % |
HMM information
| HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
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| Model details: |
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| Model length: | 324 | ||||||||||||
| Family (HMM) version: | 16 | ||||||||||||
| Download: | download the raw HMM for this family |
Species distribution
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Interactions
There is 1 interaction for this family. More...
ALADStructures
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 ALAD domain has been found. There are 72 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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