scholarly journals Dynamic properties of dipeptidyl peptidase III from Bacteroides thetaiotaomicron and the structural basis for its substrate specificity – a computational study

2017 ◽  
Vol 13 (11) ◽  
pp. 2407-2417 ◽  
Author(s):  
M. Tomin ◽  
S. Tomić
Keyword(s):  
Enzyme Activity ◽  
Substrate Specificity ◽  
Computational Study ◽  
Dynamic Properties ◽  
Dipeptidyl Peptidase ◽  
Structural Basis ◽  
Wild Type ◽  
Bacteroides Thetaiotaomicron ◽  
Human Gut

Dynamics and enzyme activity of dipeptidyl peptidase III, wild type and mutants, from the human gut symbiont Bacteroides thetaiotaomicron.

scholarly journals Correction: Dynamic properties of dipeptidyl peptidase III from Bacteroides thetaiotaomicron and the structural basis for its substrate specificity – a computational study

2017 ◽  
Vol 13 (12) ◽  
pp. 2729-2730
Author(s):  
M. Tomin ◽  
S. Tomić
Keyword(s):  
Substrate Specificity ◽  
Computational Study ◽  
Dynamic Properties ◽  
Dipeptidyl Peptidase ◽  
Structural Basis ◽  
Bacteroides Thetaiotaomicron

Correction for ‘Dynamic properties of dipeptidyl peptidase III from Bacteroides thetaiotaomicron and the structural basis for its substrate specificity – a computational study’ by M. Tomin et al., Mol. BioSyst., 2017, 13, 2407–2417.

scholarly journals Crystal structure of dipeptidyl peptidase III from the human gut symbiont Bacteroides thetaiotaomicron

PLoS ONE ◽  
2017 ◽  
Vol 12 (11) ◽  
pp. e0187295 ◽  
Author(s):  
Igor Sabljić ◽  
Nevenka Meštrović ◽  
Bojana Vukelić ◽  
Peter Macheroux ◽  
Karl Gruber ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Dipeptidyl Peptidase ◽  
Bacteroides Thetaiotaomicron ◽  
Human Gut

Reactive cysteine in the active-site motif of Bacteroides thetaiotaomicron dipeptidyl peptidase III is a regulatory residue for enzyme activity

2012 ◽  
Vol 393 (1-2) ◽  
pp. 37-46 ◽  
Author(s):  
Bojana Vukelić ◽  
Branka Salopek-Sondi ◽  
Jasminka Špoljarić ◽  
Igor Sabljić ◽  
Nevenka Meštrović ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Active Site ◽  
Sequence Similarity ◽  
Catalytic Efficiency ◽  
Basic Amino Acid ◽  
Dipeptidyl Peptidase ◽  
Pain Modulation ◽  
Binding Motif ◽  
Bacteroides Thetaiotaomicron ◽  
Active Site Motif

Abstract Dipeptidyl peptidase III (DPP III), a member of the metallopeptidase family M49, was considered as an exclusively eukaryotic enzyme involved in intracellular peptide cata­bolism and pain modulation. In 2003, new data on genome sequences revealed the first prokaryotic orthologs, which showed low sequence similarity to eukaryotic ones and a cysteine (Cys) residue in the zinc-binding motif HEXXGH. Here we report the cloning and heterologous expression of DPP III from the human gut symbiont Bacteroides thetaiotaomicron. The catalytic efficiency of bacterial DPP III for preferred synthetic substrate hydrolysis was very similar to that of the human host enzyme. Substitution of Cys450 from the active-site motif by serine did not substantially change the enzymatic activity. However, this residue was wholly responsible for the inactivation effect of sulfhydryl reagents. Molecular modeling indicated seven basic amino acid residues in the local environment of Cys450 as a possible cause for its high reactivity. Sequence analysis of 81 bacterial M49 peptidases showed conservation of the HECLGH motif in 68 primary structures with the majority of proteins lacking an active-site Cys originated from aerobic bacteria. Data obtained suggest that Cys450 of B. thetaiotaomicron DPP III is a regulatory residue for the enzyme activity.

scholarly journals Structural basis of enzyme activity regulation by the propeptide of l-lysine α-oxidase precursor from Trichoderma viride

2021 ◽  
Vol 5 ◽  
pp. 100044
Author(s):  
Masaki Kitagawa ◽  
Nanako Ito ◽  
Yuya Matsumoto ◽  
Masaya Saito ◽  
Takashi Tamura ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Trichoderma Viride ◽  
Structural Basis ◽  
Activity Regulation

Discovery of natural product ovalicin sensitive type 1 methionine aminopeptidases: molecular and structural basis

2019 ◽  
Vol 476 (6) ◽  
pp. 991-1003 ◽  
Author(s):  
Vijaykumar Pillalamarri ◽  
Tarun Arya ◽  
Neshatul Haque ◽  
Sandeep Chowdary Bala ◽  
Anil Kumar Marapaka ◽  
...  
Keyword(s):  
Natural Product ◽  
Active Site ◽  
Covalent Modification ◽  
Structural Basis ◽  
Wild Type ◽  
Methionine Aminopeptidases ◽  
Synthetic Derivative ◽  
Dynamics Simulations

Abstract Natural product ovalicin and its synthetic derivative TNP-470 have been extensively studied for their antiangiogenic property, and the later reached phase 3 clinical trials. They covalently modify the conserved histidine in Type 2 methionine aminopeptidases (MetAPs) at nanomolar concentrations. Even though a similar mechanism is possible in Type 1 human MetAP, it is inhibited only at millimolar concentration. In this study, we have discovered two Type 1 wild-type MetAPs (Streptococcus pneumoniae and Enterococcus faecalis) that are inhibited at low micromolar to nanomolar concentrations and established the molecular mechanism. F309 in the active site of Type 1 human MetAP (HsMetAP1b) seems to be the key to the resistance, while newly identified ovalicin sensitive Type 1 MetAPs have a methionine or isoleucine at this position. Type 2 human MetAP (HsMetAP2) also has isoleucine (I338) in the analogous position. Ovalicin inhibited F309M and F309I mutants of human MetAP1b at low micromolar concentration. Molecular dynamics simulations suggest that ovalicin is not stably placed in the active site of wild-type MetAP1b before the covalent modification. In the case of F309M mutant and human Type 2 MetAP, molecule spends more time in the active site providing time for covalent modification.

scholarly journals Primary structure requirements for correct sorting of the yeast mitochondrial protein ADH III to the yeast mitochondrial matrix space.

1987 ◽  
Vol 7 (1) ◽  
pp. 294-304 ◽  
Author(s):  
D Pilgrim ◽  
E T Young
Keyword(s):  
Amino Acids ◽  
Enzyme Activity ◽  
Amino Acid ◽  
Proteolytic Processing ◽  
Mitochondrial Matrix ◽  
Wild Type ◽  
Mature Form ◽  
Amino Terminal ◽  
The Matrix

Alcohol dehydrogenase isoenzyme III (ADH III) in Saccharomyces cerevisiae, the product of the ADH3 gene, is located in the mitochondrial matrix. The ADH III protein was synthesized as a larger precursor in vitro when the gene was transcribed with the SP6 promoter and translated with a reticulocyte lysate. A precursor of the same size was detected when radioactively pulse-labeled proteins were immunoprecipitated with anti-ADH antibody. This precursor was rapidly processed to the mature form in vivo with a half-time of less than 3 min. The processing was blocked if the mitochondria were uncoupled with carbonyl cyanide m-chlorophenylhydrazone. Mutant enzymes in which only the amino-terminal 14 or 16 amino acids of the presequence were retained were correctly targeted and imported into the matrix. A mutant enzyme that was missing the amino-terminal 17 amino acids of the presequence produced an active enzyme, but the majority of the enzyme activity remained in the cytoplasmic compartment on cellular fractionation. Random amino acid changes were produced in the wild-type presequence by bisulfite mutagenesis of the ADH3 gene. The resulting ADH III protein was targeted to the mitochondria and imported into the matrix in all of the mutants tested, as judged by enzyme activity. Mutants containing amino acid changes in the carboxyl-proximal half of the ADH3 presequence were imported and processed to the mature form at a slower rate than the wild type, as judged by pulse-chase studies in vivo. The unprocessed precursor appeared to be unstable in vivo. It was concluded that only a small portion of the presequence contains the necessary information for correct targeting and import. Furthermore, the information for correct proteolytic processing of the presequence appears to be distinct from the targeting information and may involve secondary structure information in the presequence.

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