Structure and Action of Urocanase

Kessler, Dirk; Rétey, János; Schulz, Georg E.

doi:10.1016/j.jmb.2004.07.028

Cited by 35 publications

(65 citation statements)

References 45 publications

(47 reference statements)

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“…Urocanase, the second enzyme in the pathway, is a homodimer with 557 amino acids in each subunit of the Pseudomonas enzyme (72,83). Like histidase, it is widely distributed within the bacterial domain, though less so in the archaeal and eukaryotic domains.…”

Section: Urocanasementioning

confidence: 99%

Regulation of the Histidine Utilization (Hut) System in Bacteria

Bender

2012

Microbiol Mol Biol Rev

122

128

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SUMMARY The ability to degrade the amino acid histidine to ammonia, glutamate, and a one-carbon compound (formate or formamide) is a property that is widely distributed among bacteria. The four or five enzymatic steps of the pathway are highly conserved, and the chemistry of the reactions displays several unusual features, including the rearrangement of a portion of the histidase polypeptide chain to yield an unusual imidazole structure at the active site and the use of a tightly bound NAD molecule as an electrophile rather than a redox-active element in urocanase. Given the importance of this amino acid, it is not surprising that the degradation of histidine is tightly regulated. The study of that regulation led to three central paradigms in bacterial regulation: catabolite repression by glucose and other carbon sources, nitrogen regulation and two-component regulators in general, and autoregulation of bacterial regulators. This review focuses on three groups of organisms for which studies are most complete: the enteric bacteria, for which the regulation is best understood; the pseudomonads, for which the chemistry is best characterized; and Bacillus subtilis , for which the regulatory mechanisms are very different from those of the Gram-negative bacteria. The Hut pathway is fundamentally a catabolic pathway that allows cells to use histidine as a source of carbon, energy, and nitrogen, but other roles for the pathway are also considered briefly here.

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Section: Urocanasementioning

confidence: 99%

Regulation of the Histidine Utilization (Hut) System in Bacteria

Bender

2012

Microbiol Mol Biol Rev

122

128

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“…It was found that there was a polypeptide modification, forming a novel catalytically essential electrophilic group. The second structure was of urocanase or HutU, also from P. putida, and the structure was determined by the same group who solved the histidase in 2004 (9). The third structure solved was the last enzyme in the histidine degradation pathway, formiminoglutamase or HutG from Vibrio cholerae, which was determined by Wu et al 5 and deposited in the Protein Data Bank under accession number 1XFK.…”

Section: 8)mentioning

confidence: 99%

A Catalytic Mechanism Revealed by the Crystal Structures of the Imidazolonepropionase from Bacillus subtilis

Bröstromer

et al. 2006

Journal of Biological Chemistry

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Imidazolonepropionase (EC 3.5.2.7) catalyzes the third step in the universal histidine degradation pathway, hydrolyzing the carbon-nitrogen bonds in 4-imidazolone-5-propionic acid to yield N-formimino-L-glutamic acid. Here we report the crystal structures of the Bacillus subtilis imidazolonepropionase and its complex at 2.0-Å resolution with substrate analog imidazole-4-acetic acid sodium (I4AA). The structure of the native enzyme contains two domains, a TIM (triose-phosphate isomerase) barrel domain with two insertions and a small ␤-sandwich domain. The TIM barrel domain is quite similar to the members of the ␣/␤ barrel metallo-dependent hydrolase superfamily, especially to Escherichia coli cytosine deaminase. A metal ion was found in the central cavity of the TIM barrel and was tightly coordinated to residues His-80, His-82, His-249, Asp-324, and a water molecule. X-ray fluorescence scan analysis confirmed that the bound metal ion was a zinc ion. An acetate ion, 6 Å away from the zinc ion, was also found in the potential active site. In the complex structure with I4AA, a substrate analog, I4AA replaced the acetate ion and contacted with Arg-89, Try-102, Tyr-152, His-185, and Glu-252, further defining and confirming the active site. The detailed structural studies allowed us to propose a zinc-activated nucleophilic attack mechanism for the hydrolysis reaction catalyzed by the enzyme.The histidine degradation pathway is highly conserved from prokaryotes to eukaryotes (1, 2). In bacteria, the histidine degradation pathway is operated by the hut (histidine utilization) genes, and the Bacillus subtilis hut operon encodes proteins in the order of HutP, HutH, HutU, HutI, HutG, HutM (3-6).There (Fig. 1A); 4) N-formimino-L-glutamic acid ϩ H 2 O 3 glutamate ϩ HCONH 2 (catalyzed by formiminoglutamase, EC 3.5.3.8).Among the four enzymes, the first three-dimensional structure determined was the 2.1-Å resolution crystal structure of histidase or HutH from Pseudomonas putida by Schulz and co-workers in 1999 (7,8). It was found that there was a polypeptide modification, forming a novel catalytically essential electrophilic group. The second structure was of urocanase or HutU, also from P. putida, and the structure was determined by the same group who solved the histidase in 2004 (9). The third structure solved was the last enzyme in the histidine degradation pathway, formiminoglutamase or HutG from Vibrio cholerae, which was determined by Wu et al. 5 and deposited in the Protein Data Bank under accession number 1XFK. The imidazolonepropionase or HutI is the only enzyme left in this pathway that has no published structural information so far, although some properties of this enzyme have been studied in Salmonella typhimurium (10), Pseudomonas fluorescens ATCC 11299 (11), rat liver (12), and other organisms during 1960s and 1970s. The maximal activity of this enzyme occurred at pH 7.4 with a narrow pH optimum, and its Michaelis constant was calculated to be 7 M (12). It was also mentioned in the literature that 1 mM EDTA could...

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“…Urocanase has been reported to present in bacteria, vertebrates/mammals, and in plant [7]. The docking studies and binding site analyses in Table 4, shows that 2-ethyl-4-methylimidazole with the highest (ACE [−111.21 kcal/mol]) while 1-nitro imidazole gave the least ACE (−26.84 kcal/mol) with that of P. putida urocanase.…”

Section: Resultsmentioning

confidence: 99%

“…In the present study, interaction with Asp443 amino acid residue has been shown by four ligands, namely, 1-ethylimidazole, 2-methyl-5-nitroimidazole, 1-nitroimidazole, and 1-vinylimidazole. Previously Kessler and coworkers (2004) reported that Asp443 amino acid residue involve in acid-base catalytic reaction, whereas Tyr52 amino acid residue stabilize the positive charge of the substrate [7].…”

Section: Resultsmentioning

confidence: 99%

“…Urocanase catalyzes the urocanate to 4-imidazolone-5-propionate (one of important intermediate compound of histidine degradation pathway). Similarly, FIGase is another enzyme belongs to arginase/ureohydrolase superfamily, which catalyzes the last step in histidine degradation pathway I through by hydrolysis the imino group of N-formimino-L-glutamate to form formamide and L-glutamate [6][7][8][9]. This prompted the present study to be carried out on 12 selected imidazole and its derivatives which are 1-imidazole, 1, 2-dimethylimidazole, 1-ethyl imidazole, 2-ethyl-4-methylimidazole, 2-isopropylimidazole, 2-isopropyl-4-nitro-1H-imidazole, 1-methylimidazole, 2-methyl-5-nitroimidazole, 2-methyl-1-vinylimidazole, 1-nitro imidazole, 1-phenyl imidazole, and 1-vinylimidazole.…”

Section: Introductionmentioning

confidence: 99%

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Predicting the Biodegradability Nature of Imidazole and Its Derivatives by Modulating Two Histidine Degradation Enzymes (Urocanase and Formiminoglutamase) Activities

Vijayakumar

Narayanaswamy

Chidambaram

2017

Asian J Pharm Clin Res

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Objectives: The biodegradation pathway of substituted imidazole ring compounds has been reported to have close analogy to the histidine degradation pathway. This prompted the present study to be carried out on 12 selected imidazole and its derivatives which are 1-imidazole, 1, 2-dimethylimidazole, 1-ethyl imidazole, 2-ethyl-4-methylimidazole, 2-isopropylimidazole, 2-Isopropyl-4-nitro-1H-imidazole, 1-methylimidazole, 2-methyl-5-nitroimidazole, 2-methyl-1-vinylimidazole, 1-nitro imidazole, 1-phenyl imidazole, and 1-vinylimidazole. Methods:The imidazole and its derivatives were evaluated on the docking behavior of urocanase and formiminoglutamase using PatchDock. In addition, molecular physicochemical, drug-likeness, absorption, distribution, metabolism, and excretion analyses (ADME) were done. Results:The molecular physicochemical analysis revealed that all the tested ligands showed nil violation and complied well with the Lipinski's rule of five. ADME analysis showed that 1-phenylimidazole alone predicated to have cytochrome P450 1A2 inhibition effect. Docking studies revealed that 1-nitroimidazole showed the least atomic contact energy with both targeted enzymes (urocanase and FIGase). Conclusion:Inhibition of both enzymes (urocanase and FIGase) might show poor biodegradability nature. Thus, we can predict biodegradability nature of imidazloe and its derivatives by modulating two histidine degradation enzymes activities.

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Structure and Action of Urocanase

Cited by 35 publications

References 45 publications

Regulation of the Histidine Utilization (Hut) System in Bacteria

Regulation of the Histidine Utilization (Hut) System in Bacteria

A Catalytic Mechanism Revealed by the Crystal Structures of the Imidazolonepropionase from Bacillus subtilis

Predicting the Biodegradability Nature of Imidazole and Its Derivatives by Modulating Two Histidine Degradation Enzymes (Urocanase and Formiminoglutamase) Activities

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