Membrane‐type 1 matrix metalloproteinase cytoplasmic tail binding protein‐1 (MTCBP‐1) acts as an eukaryotic aci‐reductone dioxygenase (ARD) in the methionine salvage pathway

Hirano, Wakako; Gotoh, Isamu; Uekita, Takamasa; Seiki, Motoharu

doi:10.1111/j.1365-2443.2005.00859.x

Cited by 30 publications

(35 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The coordinating amino acid residues seem to be well conserved also in eukaryotes (69). The MTA cycle reaction uses Fe 21 , whereas if Ni 21 is available 3-methylthiopropionate, formate, and carbon monoxide is formed instead, see Fig.…”

Section: Dioxygenasementioning

confidence: 99%

“…The dioxygenase in eukaryotes seems to be functionally conserved because the human dioxygenase could complement the corresponding yeast homologue (68,69) and, in Archaea, it seems that the dioxygenase is absent (31). In plants, the dioxygenase activity has been suggested to be regulated by combining the single polypeptide chains to oligomeric forms, which have a reduced catalytic activity (34).…”

Section: Dioxygenasementioning

confidence: 99%

See 1 more Smart Citation

Metabolic characteristics and importance of the universal methionine salvage pathway recycling methionine from 5′‐methylthioadenosine

2009

View full text Add to dashboard Cite

SummaryThe methionine salvage pathway, also called the 5 0 -methylthioadenosine (MTA) cycle, recycles the sulfur of MTA, which is a by-product in the biosyntheses of polyamine and the plant hormone ethylene. MTA is first converted to 5 0 -methylthioribose-1-phosphate either by MTA phosphorylase or the combined action of MTA nucleosidase and 5 0 -methylthioribose kinase. Subsequently, five additional enzymatic steps, catalyzed by four or five proteins, will form 4-methylthio-2-oxobutyrate, the deaminated form of methionine. The final transamination is achieved by transaminases active in the amino acid biosynthesis. This pathway is present with some variations in all types of organisms and seems to be designed for a quick removal of MTA achieved by high affinities of the first enzymes. During evolution some enzymes have attained additional functions, like a proposed role in nuclear mRNA processing by the aci-reductone dioxygenase. For others the function seems to be lost due to conditions in specific ecological niches, such as, presence of sulfur and/or absence of oxygen resulting in that, for example, Escherichia coli is lacking a functional pathway. The pathway is regulated as response to sulfur availability and take part in the regulation of polyamine synthesis. Some of the enzymes in the pathway show separate specificities in different organisms and some others are unique for groups of bacteria and parasites. Thus, promising targets for antimicrobial agents have been identified. Other medical topics to which this pathway has connections are cancer, apoptosis, and inflammatory response.

show abstract

Section: Dioxygenasementioning

confidence: 99%

Section: Dioxygenasementioning

confidence: 99%

Metabolic characteristics and importance of the universal methionine salvage pathway recycling methionine from 5′‐methylthioadenosine

2009

View full text Add to dashboard Cite

show abstract

“…Our analysis indicated that during infection P. brasiliensis seems to be able to synthesize asparagine, providing, in addition to glutamine, another site for transient storage of nitrogen. The novel transcript encoding aci-reductone dioxygenase suggests the presence of the methionine salvage pathway cycle (Hirano et al, 2005) providing additional methionine, which could be scarce in the host environment. Overall, the presumed increase in synthesis of the amino acids listed above implies that those compounds are not present at sufficient levels in host tissue to support growth of P. brasiliensis.…”

Section: Transcriptome Of P Brasiliensis During Infectionmentioning

confidence: 99%

Transcriptome profiling of Paracoccidioides brasiliensis yeast-phase cells recovered from infected mice brings new insights into fungal response upon host interaction

et al. 2007

View full text Add to dashboard Cite

Paracoccidioides brasiliensis is a fungal human pathogen with a wide distribution in Latin America. It causes paracoccidioidomycosis, the most widespread systemic mycosis in Latin America. Although gene expression in P. brasiliensis had been studied, little is known about the genome sequences expressed by this species during the infection process. To better understand the infection process, 4934 expressed sequence tags (ESTs) derived from a non-normalized cDNA library from P. brasiliensis (isolate Pb01) yeast-phase cells recovered from the livers of infected mice were annotated and clustered to a UniGene (clusters containing sequences that represent a unique gene) set with 1602 members. A large-scale comparative analysis was performed between the UniGene sequences of P. brasiliensis yeast-phase cells recovered from infected mice and a database constructed with sequences of the yeast-phase and mycelium transcriptome (isolate Pb01) (https://dna.biomol.unb.br/Pb/), as well as with all public ESTs available at GenBank, including sequences of the P. brasiliensis yeast-phase transcriptome (isolate Pb18) (http:// www.ncbi.nlm.nih.gov/). The focus was on the overexpressed and novel genes. From the total, 3184 ESTs (64.53 %) were also present in the previously described transcriptome of yeast-form and mycelium cells obtained from in vitro cultures (https://dna.biomol.unb.br/Pb/) and of those, 1172 ESTs (23.75 % of the described sequences) represented transcripts overexpressed during the infection process. Comparative analysis identified 1750 ESTs (35.47 % of the total), comprising 649 UniGene sequences representing novel transcripts of P. brasiliensis, not previously described for this isolate or for other isolates in public databases. KEGG pathway mapping showed that the novel and overexpressed transcripts represented standard metabolic pathways, including glycolysis, amino acid biosynthesis, lipid and sterol metabolism. The unique and divergent representation of transcripts in the cDNA library of yeast cells recovered from infected mice suggests differential gene expression in response to the host milieu.Abbreviations: EST, expressed sequence tag; KEGG, Kyoto Encyclopedia of Gene and Genomes; sqRT-PCR, semiquantitative RT-PCR.3These authors contributed equally to this work.The GenBank/EMBL/DDBJ accession numbers for the ESTs of Paracoccidioides brasiliensis identified in this study are EST1487-EST6420.Two supplementary tables listing the overexpressed and novel genes identified during this study and supplementary material describing the EST dataset analysed are available with the online version of this paper. Microbiology

show abstract

“…Based on the evidence of XAS, site-directed mutagenesis and isothermal calorimetry experiments described in this paper as well as evidence from other laboratories and our own previous work (14,18), we conclude that the same amino acid residues, His 96, His 98, Glu 102 and His 140 provide the protein-based ligands for the metal in both Fe-and Ni-bound forms of ARD, and that both metals are bound in approximately octahedral geometry, with solvent-derived ligands providing the remainder of the coordination sphere. This conclusion implies that relatively subtle differences between the two metal-protein complexes are amplified by the surrounding protein structure, giving two enzymes of different structures and activities from a single polypeptide.…”

mentioning

confidence: 99%

Characterization of Metal Binding in the Active Sites of Acireductone Dioxygenase Isoforms from Klebsiella ATCC 8724

Chai

Dang

et al. 2008

Biochemistry

View full text Add to dashboard Cite

The two acireductone dioxygenase (ARD) isozymes from the methionine salvage pathway of Klebsiella ATCC 8724 present an unusual case in which two enzymes with different structures and distinct activities towards their common substrates (1,2-dihydroxy-3-oxo-5-(methylthio)pent-1-ene and dioxygen) are derived from the same polypeptide chain. Structural and functional differences between the two isozymes are determined by the type of M +2 metal ion bound in the active site. The Ni +2 -bound NiARD catalyzes an off-pathway shunt from the methionine salvage pathway leading to the production of formate, methylthiopropionate and carbon monoxide, while the Fe +2 -bound FeARD' catalyzes the on-pathway formation of methionine precursor 2-keto-4-methylthiobutyrate and formate. Four potential protein-based metal ligands were identified by sequence homology and structural considerations. Based on the results of site-directed mutagenesis experiments, X-ray absorption spectroscopy (XAS) and isothermal calorimetry measurements, it is concluded that the same four residues, His 96, His 98, Glu 102 and His 140, provide the protein-based ligands for the metal in both the Ni-and Fe-containing forms of the enzyme, and subtle differences in the local backbone conformations trigger the observed structural and functional differences between the FeARD' and NiARD isozymes. Furthermore, both forms of the enzyme bind their respective metals with pseudo-octahedral geometry, and both may lose a His ligand upon binding of substrate under anaerobic conditions. However, mutations at two conserved non-ligand acidic residues, Glu 95 and Glu 100, result in low metal contents for the mutant proteins as isolated, suggesting that some of the conserved charged residues may aid in transfer of metal from in vivo sources or prevent the loss of metal to stronger chelators. The Glu 100 mutant reconstitutes readily but has low activity. Mutation of Asp 101 results in an active enzyme that incorporates metal in vivo but shows evidence of mixed forms.* To whom correspondence should be addressed: pochapsk@brandeis.edu, phone 781−736−2559, fax 781−736−2516. e Current address: Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, 70 Ship Street, GE3, Providence, RI, 02912 f Current address: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Dr., Room 1007, Indianapolis IN 46202 g This work was supported in part by USPHS grant (R01-GM067786 TCP). Acknowledgment is made to the donors of The American Chemical Society Petroleum Research Fund for partial support (MJM). Trainee funding (SCC) was provided by the NIH-Chemistry Biology Interface Program, T32-GM08515. XAS data collection at the National Synchrotron Light Source at Brookhaven National Laboratory was supported by the U.S. Department of Energy, Division of Materials Sciences and Division of Chemical Sciences. Beamline X9B at NSLS is supported in part by the NIH.Supporting information available Fits for resting state and ES...

show abstract

Membrane‐type 1 matrix metalloproteinase cytoplasmic tail binding protein‐1 (MTCBP‐1) acts as an eukaryotic aci‐reductone dioxygenase (ARD) in the methionine salvage pathway

Abstract: MTCBP-1 was identified as a protein that binds

Cited by 30 publications

References 20 publications

Metabolic characteristics and importance of the universal methionine salvage pathway recycling methionine from 5′‐methylthioadenosine

Metabolic characteristics and importance of the universal methionine salvage pathway recycling methionine from 5′‐methylthioadenosine

Transcriptome profiling of Paracoccidioides brasiliensis yeast-phase cells recovered from infected mice brings new insights into fungal response upon host interaction

Characterization of Metal Binding in the Active Sites of Acireductone Dioxygenase Isoforms from Klebsiella ATCC 8724

Contact Info

Product

Resources

About