Urocanase

Crystal structure of Urocanase from B. subtilis.

Identifiers

Symbol

Urocanase

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Imidazol-4-one-5-propionic acid

Urocanase^[1] (also known as imidazolonepropionate hydrolase or urocanate hydratase) is the enzyme that catalyzes the second step in the degradation of histidine, the hydration of urocanate into imidazolonepropionate.

Urocanase is coded for by the UROC1 gene, located on the 3rd chromosome in humans.^[2] The protein itself is composed of 676 amino acids which then fold, producing the final product which has 2 identical subunits, making the enzyme a homodimer.

To catalyze the hydrolysis of urocanate in the catabolic pathway of L-histidine the enzyme utilizes it's two NAD+ (Nicotinamide Adnene Dinucleotide) groups. The NAD+ groups act as electrophiles, attaching to the top carbon of the urocanate which leads to sigmatropic rearrangement of the urocanate molecule.^[3] This rearrangement allows for the addition of a water molecule, converting the urocanate into 4,5-dihydro-4-oxo-5-imidazolepropanoate.^[4]

urocanate + H₂O

\rightleftharpoons

4,5-dihydro-4-oxo-5-imidazolepropanoate

Inherited deficiency of urocanase leads to elevated levels of urocanic acid in the urine, a condition known as urocanic aciduria.

Urocanase is found in some bacteria (gene hutU), in the liver of many vertebrates and has also been found in the plant Trifolium repens (white clover). Urocanase is a protein of about 60 Kd, it binds tightly to NAD⁺ and uses it as an electrophil cofactor. A conserved cysteine has been found to be important for the catalytic mechanism and could be involved in the binding of the NAD⁺.

References

↑ Retey J (1994). "The urocanase story: a novel role of NAD+ as electrophile". Arch. Biochem. Biophys. 314 (1): 1–16. doi:10.1006/abbi.1994.1405. PMID 7944380.
↑ "http://www.genecards.org/cgi-bin/carddisp.pl?gene=UROC1". www.genecards.org. Retrieved 2016-11-03. External link in |title= (help)
↑ Kevin Tokoph (2014-12-23), Urocanate Hydratase Mechanism, retrieved 2016-11-03
↑ "Mutations in the urocanase gene UROC1 are associated with urocanic aciduria" (PDF). Bitstream.

External links

Urocanate Hydratase at the US National Library of Medicine Medical Subject Headings (MeSH)
EC 4.2.1.49

Metabolism: Protein metabolism, synthesis and catabolism enzymes

Essential amino acids are in Capitals

K→acetyl-CoA

LYSINE→	Saccharopine dehydrogenase Glutaryl-CoA dehydrogenase

LEUCINE→	Branched chain aminotransferase Branched-chain alpha-keto acid dehydrogenase complex Isovaleryl coenzyme A dehydrogenase Methylcrotonyl-CoA carboxylase Methylglutaconyl-CoA hydratase 3-hydroxy-3-methylglutaryl-CoA lyase

TRYPTOPHAN→	Indoleamine 2,3-dioxygenase/Tryptophan 2,3-dioxygenase Arylformamidase Kynureninase 3-hydroxyanthranilate oxidase Aminocarboxymuconate-semialdehyde decarboxylase Aminomuconate-semialdehyde dehydrogenase

PHENYLALANINE→tyrosine→	(see below)

G→pyruvate
→citrate

glycine→serine→	Serine hydroxymethyltransferase Serine dehydratase glycine→creatine: Guanidinoacetate N-methyltransferase Creatine kinase

alanine→	Alanine transaminase

cysteine→	D-cysteine desulfhydrase

threonine→	L-threonine dehydrogenase

G→glutamate→
α-ketoglutarate

HISTIDINE→	Histidine ammonia-lyase Urocanate hydratase Formiminotransferase cyclodeaminase

proline→	Proline oxidase Pyrroline-5-carboxylate reductase 1-Pyrroline-5-carboxylate dehydrogenase/ALDH4A1 PYCR1

arginine→	Ornithine aminotransferase Ornithine decarboxylase Agmatinase

→alpha-ketoglutarate→TCA	Glutamate dehydrogenase

Other	cysteine+glutamate→glutathione: Gamma-glutamylcysteine synthetase Glutathione synthetase Gamma-glutamyl transpeptidase glutamate→glutamine: Glutamine synthetase Glutaminase

G→propionyl-CoA→
succinyl-CoA

VALINE→	Branched chain aminotransferase Branched-chain alpha-keto acid dehydrogenase complex Enoyl-CoA hydratase 3-hydroxyisobutyryl-CoA hydrolase 3-hydroxyisobutyrate dehydrogenase Methylmalonate semialdehyde dehydrogenase

ISOLEUCINE→	Branched chain aminotransferase Branched-chain alpha-keto acid dehydrogenase complex 3-hydroxy-2-methylbutyryl-CoA dehydrogenase

METHIONINE→	generation of homocysteine: Methionine adenosyltransferase Adenosylhomocysteinase regeneration of methionine: Methionine synthase/Homocysteine methyltransferase Betaine-homocysteine methyltransferase conversion to cysteine: Cystathionine beta synthase Cystathionine gamma-lyase

THREONINE→	Threonine aldolase

→succinyl-CoA→TCA	Propionyl-CoA carboxylase Methylmalonyl CoA epimerase Methylmalonyl-CoA mutase

G→fumarate

PHENYLALANINE→tyrosine→	Phenylalanine hydroxylase Tyrosine aminotransferase 4-Hydroxyphenylpyruvate dioxygenase Homogentisate 1,2-dioxygenase Fumarylacetoacetate hydrolase tyrosine→melanin: Tyrosinase

G→oxaloacetate

asparagine→aspartate→	Asparaginase/Asparagine synthetase Aspartate transaminase

Carbon-oxygen lyases (EC 4.2) (primarily dehydratases)

4.2.1: Hydro-Lyases	Carbonic anhydrase Fumarase Aconitase Enolase Alpha Enolase 2 Enoyl-CoA hydratase/3-Hydroxyacyl ACP dehydrase Methylglutaconyl-CoA hydratase Tryptophan synthase Cystathionine beta synthase Porphobilinogen synthase 3-Isopropylmalate dehydratase Urocanase Uroporphyrinogen III synthase Nitrile hydratase

4.2.2: Acting on polysaccharides	Hyaluronate lyase

4.2.3: Acting on phosphates	Threonine synthase

4.2.99: Other	Carboxymethyloxysuccinate lyase

Enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Enzyme kinetics Lineweaver–Burk plot Michaelis–Menten kinetics

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list)

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