Disease relevance of hemD

• The functions of the protein coded by cobA + hemD were established by heterologous expression in Escherichia coli [1].
• A gene, cobA + hemD, from Selenomonas ruminantium encodes a bifunctional enzyme involved in the synthesis of vitamin B12 [1].
• The Pseudomonas aeruginosa homologs of hemC and hemD are linked to the gene encoding the regulator of mucoidy AlgR [2].
• A systematic analysis of the mutations of the uroporphyrinogen III synthase gene in congenital erythropoietic porphyria [3].
• Expression, purification and characterisation of the product from the Bacillus subtilis hemD gene, uroporphyrinogen III synthase [4].

High impact information on hemD

• Mutagenesis identifies a conserved tyrosine residue important for the activity of uroporphyrinogen III synthase from Anacystis nidulans [5].
• Three new missense mutations of UROIIIS coding sequence (H173Y, Q187P and P248Q) have been observed together with 8 known mutations [3].
• As an alternative, the mutation can be determined by sequencing the UROIIIS cDNA of the patient, using the RT-PCR technique on RNAs when a lymphoblastoid cell line can be established [3].
• Porphobilinogen deaminase (hydroxymethylbilane synthase) and uroporphyrinogen III synthase (uroporphyrinogen III cosynthase) catalyze the transformation of four molecules of porphobilinogen, via the 1-hydroxymethylbilane, preuroporphyrinogen, into uroporphyrinogen III [6].
• Porphobilinogen deaminase and uroporphyrinogen III synthase: structure, molecular biology, and mechanism [6].

Biological context of hemD

• Two open reading frames were found immediately upstream of hemD [7].
• Following thermal induction of transcription, the resulting plasmid (pPS21) directed the synthesis of uroporphyrinogen III synthase [4].

Associations of hemD with chemical compounds

• Studies based on amino acid modifications suggest that arginine, lysine and probably histidine residues are essential for the activity of uroporphyrinogen III synthase [4].
• The biosynthesis of the uroporphyrinogen III macrocycle from porphobilinogen requires the sequential participation of two enzymes--porphobilinogen deaminase (1-hydroxymethylbilane synthase, EC 4.3.1.8) and uroporphyrinogen III synthase (cosynthase, EC 4.2.1.75) [8].

Analytical, diagnostic and therapeutic context of hemD

• Uroporphyrinogen III synthase from the cyanobacterium Anacystis nidulans was overproduced in Escherichia coli and analyzed by site specific mutagenesis [5].

References