Mechanism of Inactivation of Ornithine Transcarbamoylase by N δ-(N′-Sulfodiaminophosphinyl)-l-ornithine, a True Transition State Analogue?

Langley, David B.; Templeton, Matthew D.; Fields, Barry A.; Mitchell, Robin E.; Collyer, Charles A.

doi:10.1074/jbc.m000585200

Cited by 40 publications

(60 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5 These trimers are generally referred to as "catalytic trimers," as they constitute the basic catalytic structural unit in OTCs and, more generally, amongst the carbamoyltransferases. 11 Representative crystal structures of aOTCs from several sources have been determined: human aOTC complexed with the bisubstrate analog N-(phosphonacetyl)-Lornithine (PALO) 12 and more recently with CP and the inhibitor L-norvaline; 13 unliganded aOTC from Escherichia coli 14 as well as complexes with PALO 15 and with N δ -(N-sulfodiaminophosphinyl)-L-ornithine; 16 aOTC from Pyrococcus furiosus; 17 and, finally, aOTC from Mycobacterium tuberculosis, both unliganded and in complex with CP and L-norvaline. 18 Interestingly, aOTC from P. furiosus, despite being an anabolic enzyme, is a dodecamer assembly 17 and shows no allosteric regulation.…”

Section: Introductionmentioning

confidence: 99%

Crystal Structure of the Hexameric Catabolic Ornithine Transcarbamylase from Lactobacillus hilgardii: Structural Insights into the Oligomeric Assembly and Metal Binding

Rivas

Fox

Ângulo

et al. 2009

Journal of Molecular Biology

View full text Add to dashboard Cite

Catabolic ornithine transcarbamylase (cOTC; EC 2.1.3.3) catalyzes the formation of ornithine (ORN) and carbamoyl phosphate from citrulline, which constitutes the second step of the degradation of arginine via the arginine deiminase pathway. Here, we report the crystal structure of cOTC from the lactic acid bacteria Lactobacillus hilgardii (Lh-cOTC) refined to 2.1 A resolution. The structure reveals that Lh-cOTC forms a hexameric assembly, which was also confirmed by gel-filtration chromatography and analytical ultracentrifugation. The homohexamer, with 32 point group symmetry, represents a new oligomeric state within the members of the ornithine transcarbamylase family that are typically homotrimeric or homododecameric. The C-terminal end from each subunit constitutes a key structural element for the stabilization of the hexameric assembly in solution. Additionally, the structure reveals, for the first time in the ornithine transcarbamylase family, a metal-binding site located at the 3-fold molecular symmetry axis of each trimer.

show abstract

Section: Introductionmentioning

confidence: 99%

Crystal Structure of the Hexameric Catabolic Ornithine Transcarbamylase from Lactobacillus hilgardii: Structural Insights into the Oligomeric Assembly and Metal Binding

Rivas

Fox

Ângulo

et al. 2009

Journal of Molecular Biology

View full text Add to dashboard Cite

show abstract

“…This halo results from the action of a non-hostspecific toxin known as phaseolotoxin [N ␦ (NЈ-sulfodiaminophosphinyl)-ornithyl-alanyl-homoarginine] (22,25). Phaseolotoxin is a reversible inhibitor of the enzyme ornithine carbamoyltransferase, (OCTase) (EC 2.1.3.3) (7,17) that catalyzes the formation of citrulline from ornithine and carbamoylphosphate in the sixth step of the arginine biosynthetic pathway. In planta phaseolotoxin is readily cleaved by peptidases to release N ␦ (NЈ-sulfodiaminophosphinyl)-ornithine (PSOrn), the major toxic chemical species present in diseased leaf tissue (23).…”

mentioning

confidence: 99%

Functional Characterization of the Gene Cluster from Pseudomonas syringae pv. phaseolicola NPS3121 Involved in Synthesis of Phaseolotoxin

Aguilera¹,

López‐López

Nieto³

et al. 2007

J Bacteriol

View full text Add to dashboard Cite

Pseudomonas syringae pv. phaseolicola is the causal agent of halo blight disease of beans (Phaseolus vulgaris L.), which is characterized by water-soaked lesions surrounded by a chlorotic halo resulting from the action of a non-host-specific toxin known as phaseolotoxin. This phytotoxin inhibits the enzyme ornithine carbamoyltransferase involved in arginine biosynthesis. Different evidence suggested that genes involved in phaseolotoxin production were clustered. Two genes had been previously identified in our laboratory within this cluster: argK, which is involved in the immunity of the bacterium to its own toxin, and amtA, which is involved in the synthesis of homoarginine. We sequenced the region around argK and amtA in P. syringae pv. phaseolicola NPS3121 to determine the limits of the putative phaseolotoxin gene cluster and to determine the transcriptional pattern of the genes comprising it. We report that the phaseolotoxin cluster (Pht cluster) is composed of 23 genes and is flanked by insertion sequences and transposases. The mutation of 14 of the genes within the cluster lead to a Tox ؊ phenotype for 11 of them, while three mutants exhibited low levels of toxin production. The analysis of fusions of selected DNA fragments to uidA, Northern probing, and reverse transcription-PCR indicate the presence of five transcriptional units, two monocistronic and three polycistronic; one is internal to a larger operon. The site for transcription initiation has been determined for each promoter, and the putative promoter regions were identified. Preliminary results also indicate that the gene product of phtL is involved in the regulation of the synthesis of phaseolotoxin.Pseudomonas syringae pv. phaseolicola is the causal agent of halo blight disease of beans (Phaseolus vulgaris L.), which is characterized by water-soaked lesions surrounded by a chlorotic halo (23). This halo results from the action of a non-hostspecific toxin known as phaseolotoxin [N ␦

show abstract

“…1b), of which the latter is a competitive inhibitor of the enzyme 14 and a better analogue than PALO. OTC structures from microorganisms such as Escherichia coli, [15][16][17] Pseudomonas aeruginosa (Pae) 18 and Pyrococcus furiosus (Pfu) 19,20 have also been determined. In the present study, structures of both forms of Mtb OTC have been compared with the high-resolution structures of OTC and ATC available in the literature.…”

Section: Introductionmentioning

confidence: 99%

The Crystal Structures of Ornithine Carbamoyltransferase from Mycobacterium tuberculosis and Its Ternary Complex with Carbamoyl Phosphate and l-Norvaline Reveal the Enzyme's Catalytic Mechanism

Sankaranarayanan

Cherney

et al. 2008

Journal of Molecular Biology

View full text Add to dashboard Cite

Mechanism of Inactivation of Ornithine Transcarbamoylase by N δ-(N′-Sulfodiaminophosphinyl)-l-ornithine, a True Transition State Analogue?

Cited by 40 publications

References 43 publications

Crystal Structure of the Hexameric Catabolic Ornithine Transcarbamylase from Lactobacillus hilgardii: Structural Insights into the Oligomeric Assembly and Metal Binding

Crystal Structure of the Hexameric Catabolic Ornithine Transcarbamylase from Lactobacillus hilgardii: Structural Insights into the Oligomeric Assembly and Metal Binding

Functional Characterization of the Gene Cluster from Pseudomonas syringae pv. phaseolicola NPS3121 Involved in Synthesis of Phaseolotoxin

The Crystal Structures of Ornithine Carbamoyltransferase from Mycobacterium tuberculosis and Its Ternary Complex with Carbamoyl Phosphate and l-Norvaline Reveal the Enzyme's Catalytic Mechanism

Contact Info

Product

Resources

About