Possible role of inter-domain salt bridges in oligopeptidase B from Trypanosoma brucei: critical role of Glu172 of non-catalytic  -propeller domain in catalytic activity and Glu490 of catalytic domain in stability of OPB

2013 ◽  
Vol 154 (5) ◽  
pp. 465-473 ◽  
Author(s):  
J. Fukumoto ◽  
N. I. M. Ismail ◽  
M. Kubo ◽  
K. Kinoshita ◽  
M. Inoue ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Trypanosoma Brucei ◽  
Catalytic Domain ◽  
Critical Role ◽  
Salt Bridges ◽  
Oligopeptidase B

Identification of the Critical Role of Tyr-194 in the Catalytic Activity of a Novel N-Acyl-Homoserine Lactonase from Marine Bacillus cereus Strain Y2

2006 ◽  
Vol 53 (4) ◽  
pp. 346-350 ◽  
Author(s):  
X. Lu ◽  
Y. Yuan ◽  
X.-L. Xue ◽  
G.-P. Zhang ◽  
S.-N. Zhou
Keyword(s):  
Catalytic Activity ◽  
Bacillus Cereus ◽  
Critical Role

scholarly journals Mutating His29, His125, His133 or His158 abolishes glycosylphosphatidylinositol-specific phospholipase D catalytic activity

2005 ◽  
Vol 391 (2) ◽  
pp. 285-289 ◽  
Author(s):  
Nandita S. Raikwar ◽  
Rosario F. Bowen ◽  
Mark A. Deeg
Keyword(s):  
Catalytic Activity ◽  
Phospholipase D ◽  
Catalytic Domain ◽  
Computer Modelling ◽  
Critical Role ◽  
Biochemical Properties ◽  
Catalytic Site ◽  
Wild Type ◽  
Histidine Residues ◽  
Hydrolysis Of

Glycosylphosphatidylinositol (GPI)-specific phospholipase D (GPI-PLD) specifically cleaves GPIs. This phospholipase D is a secreted protein consisting of two domains: an N-terminal catalytic domain and a predicted C-terminal β-propeller. Although the biochemical properties of GPI-PLD have been extensively studied, its catalytic site has not been identified. We hypothesized that a histidine residue(s) may play a critical role in the catalytic activity of GPI-PLD, based on the observations that (i) Zn2+, which utilizes histidine residues for binding, is required for GPI-PLD catalytic activity, (ii) a phosphohistidine intermediate is involved in phospholipase D hydrolysis of phosphatidylcholine, (iii) computer modelling suggests a catalytic site containing histidine residues, and (iv) our observation that diethyl pyrocarbonate, which modifies histidine residues, inhibits GPI-PLD catalytic activity. Individual mutation of the ten histidine residues to asparagine in the catalytic domain of murine GPI-PLD resulted in three general phenotypes: not secreted or retained (His56 or His88), secreted with catalytic activity (His34, His81, His98 or His219) and secreted without catalytic activity (His29, His125, His133 or His158). Changing His133 but not His29, His125 or His158 to Cys resulted in a mutant that retained catalytic activity, suggesting that at least His133 is involved in Zn2+ binding. His133 and His158 also retained the biochemical properties of wild-type GPI-PLD including trypsin cleavage pattern and phosphorylation by protein kinase A. Hence, His29, His125, His133 and His158 are required for GPI-PLD catalytic activity.

scholarly journals Core–shell Au@AuAg nano-peanuts for the catalytic reduction of 4-nitrophenol: critical role of hollow interior and broken shell structure

2020 ◽  
Vol 2 (10) ◽  
pp. 4841-4852
Author(s):  
Varsha Thambi ◽  
Abhay Raj Singh Gautam ◽  
Saumyakanti Khatua
Keyword(s):  
Catalytic Activity ◽  
Shell Structure ◽  
Catalytic Reduction ◽  
Critical Role ◽  
Core Shell ◽  
Hole Size ◽  
Hollow Interior

We report the synthesis and enhanced catalytic activity of broken-shell nano-peanuts with variable hole size.

Insights into stabilizing interactions in the distorted domain-swapped dimer ofSalmonella typhimuriumsurvival protein

2015 ◽  
Vol 71 (9) ◽  
pp. 1812-1823 ◽  
Author(s):  
Yamuna Kalyani Mathiharan ◽  
H. S. Savithri ◽  
M. R. N. Murthy
Keyword(s):  
Hydrogen Bond ◽  
Catalytic Activity ◽  
Salt Bridge ◽  
Salt Bridges ◽  
X Ray ◽  
Dimeric Interface ◽  
Distorted Structure ◽  
Dimeric Protein ◽  
The Stability

The survival protein SurE fromSalmonella typhimurium(StSurE) is a dimeric protein that functions as a phosphatase. SurE dimers are formed by the swapping of a loop with a pair of β-strands and a C-terminal helix between two protomers. In a previous study, the Asp230 and His234 residues were mutated to Ala to abolish a hydrogen bond that was thought to be crucial for C-terminal helix swapping. These mutations led to functionally inactive and distorted dimers in which the two protomers were related by a rotation of 167°. New salt bridges involving Glu112 were observed in the dimeric interface of the H234A and D230A/H234A mutants. To explore the role of these salt bridges in the stability of the distorted structure, E112A, E112A/D230A, E112A/H234A, E112A/D230A/H234A, R179L/H180A/H234A and E112A/R179L/H180A/H234A mutants were constructed. X-ray crystal structures of the E112A, E112A/H234A and E112A/D230A mutants could be determined. The dimeric structures of the E112A and E112A/H234A mutants were similar to that of native SurE, while the E112A/D230A mutant had a residual rotation of 11° between theBchains upon superposition of theAchains of the mutant and native dimers. The native dimeric structure was nearly restored in the E112A/H234A mutant, suggesting that the new salt bridge observed in the H234A and D230A/H234A mutants was indeed responsible for the stability of their distorted structures. Catalytic activity was also restored in these mutants, implying that appropriate dimeric organization is necessary for the activity of SurE.

Abstract 4339: Critical role of Dnmt3b catalytic activity in prevention of oncogene-induced leukemias and lymphomas

2019 ◽  
Author(s):  
Katarina Lopusna ◽  
Pawel Nowialis ◽  
Staci L. Haney ◽  
Ajay Abraham ◽  
Jana Opavska ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Critical Role ◽  
Leukemias And Lymphomas

Effect of matrix metallopeptidase 13 (MMP13) on multiple myeloma (MM) cells, osteoclast (OCL) activity, and bone resorption.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8099-8099
Author(s):  
Jing Fu ◽  
Shirong Li ◽  
Rentian Feng ◽  
Mei Hua Jin ◽  
Farideh Sabeh ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Bone Resorption ◽  
Bone Disease ◽  
Critical Role ◽  
Site Directed Mutagenesis ◽  
Hek293 Cells ◽  
Bone Lesions ◽  
Lytic Lesions

8099 Background: MM cells produce OCL-activating factors that induce excessive bone resorption resulting in lytic lesions. The role of MMPs in invasion/progression of solid tumors is well-known, but its function in MM has not been well elucidated. Our group has shown that MMP13 is highly expressed in primary MM cells and in sera of MM patients. Levels of MMP13 significantly correlate with the extent of bone disease. MMP13 is induced by IL-6 via AP-1 activation in MM cells and enhances fusion of OCL precursors resulting in excessive bone resorption. OCL formation using MNCs of mmp-13-/- mice resulted in a fusion defect, significantly decreased OCL size and activity, which could be reversed by exogenous MMP13 (ASH 2009, IMW 2011). Methods: Methods will be presented in the Results section. Results: RT-PCR and western blotting revealed that IL-6 treatment of MM cells induced MMP13 transcription (30-fold) and secretion (>1000-fold). Protein expression of the AP-1 members c-Jun and c-Fos was induced by IL-6, which correlated with MMP13 upregulation. Our data further indicate that the catalytic activity of MMP13 is not required to enhance OCL formation and bone resorption. To prove this, we generated the MMP13 activity-dead mutation MMP13-E223A construct by site-directed mutagenesis PCR-based cloning. The mutated protein was overexpressed in HEK293 cells and purified from the supernatant to confirm whether loss of catalytic activity blocks MMP13 function. To further investigate the in vivo role of MMP13 in MM bone disease, MMP13 expression was knocked down (KD) in murine 5TGM1-MM cells by pKLO. 1 puro lentiviral infection containing sh-RNA targeting mouse MMP13 sequence. MMP13-KD 5TGM1-MM cells or WT-5TGM1-MM cells were intratibially injected into RAG2-/- mice. Development of lytic bone lesions are monitored by micro-QCT and data will be available at the time of presentation. Conclusions: Our data suggest that MMP13, secreted by MM cells, plays a critical role in the development of lytic lesions. Targeting MMP13 represents a promising approach to treat or to prevent bone disease in MM.

scholarly journals Structural Insight into the Critical Role of the N-Terminal Region in the Catalytic Activity of Dual-Specificity Phosphatase 26

PLoS ONE ◽  
2016 ◽  
Vol 11 (9) ◽  
pp. e0162115 ◽  
Author(s):  
Eun-Young Won ◽  
Sang-Ok Lee ◽  
Dong-Hwa Lee ◽  
Daeyoup Lee ◽  
Kwang-Hee Bae ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Critical Role ◽  
Terminal Region ◽  
Dual Specificity Phosphatase ◽  
Dual Specificity ◽  
Structural Insight ◽  
Insight Into

A critical role for highly conserved Glu610 residue of oligopeptidase B from Trypanosoma brucei in thermal stability

2009 ◽  
Vol 147 (2) ◽  
pp. 201-211 ◽  
Author(s):  
N. I. Mohd Ismail ◽  
T. Yuasa ◽  
K. Yuasa ◽  
Y. Nambu ◽  
M. Nisimoto ◽  
...  
Keyword(s):  
Thermal Stability ◽  
Trypanosoma Brucei ◽  
Critical Role ◽  
Oligopeptidase B

Abstract 4339: Critical role of Dnmt3b catalytic activity in prevention of oncogene-induced leukemias and lymphomas

2019 ◽  
Author(s):  
Katarina Lopusna ◽  
Pawel Nowialis ◽  
Staci L. Haney ◽  
Ajay Abraham ◽  
Jana Opavska ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Critical Role ◽  
Leukemias And Lymphomas
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