Systematic investigation of PRMT6 substrate recognition reveals broad specificity with a preference for an RG motif or basic and bulky residues

FEBS Journal ◽  
2021 ◽  
Author(s):  
Joshua J. Hamey ◽  
Sinja Rakow ◽  
Caroline Bouchard ◽  
Johanna M. Senst ◽  
Peter Kolb ◽  
...  

2020 ◽  
Vol 295 (15) ◽  
pp. 5012-5021 ◽  
Author(s):  
Fernanda Mandelli ◽  
Mariana Abrahão Bueno de Morais ◽  
Evandro Antonio de Lima ◽  
Leane Oliveira ◽  
Gabriela Felix Persinoti ◽  
...  

β-Mannanases from the glycoside hydrolase 26 (GH26) family are retaining hydrolases that are active on complex heteromannans and whose genes are abundant in rumen metagenomes and metatranscriptomes. These enzymes can exhibit distinct modes of substrate recognition and are often fused to carbohydrate-binding modules (CBMs), resulting in a molecular puzzle of mechanisms governing substrate preference and mode of action that has not yet been pieced together. In this study, we recovered a novel GH26 enzyme with a CBM35 module linked to its N terminus (CrMan26) from a cattle rumen metatranscriptome. CrMan26 exhibited a preference for galactomannan as substrate and the crystal structure of the full-length protein at 1.85 Å resolution revealed a unique orientation of the ancillary domain relative to the catalytic interface, strategically positioning a surface aromatic cluster of the ancillary domain as an extension of the substrate-binding cleft, contributing to galactomannan preference. Moreover, systematic investigation of nonconserved residues in the catalytic interface unveiled that residues Tyr195 (−3 subsite) and Trp234 (−5 subsite) from distal negative subsites have a key role in galactomannan preference. These results indicate a novel and complex mechanism for substrate recognition involving spatially remote motifs, distal negative subsites from the catalytic domain, and a surface-associated aromatic cluster from the ancillary domain. These findings expand our molecular understanding of the mechanisms of substrate binding and recognition in the GH26 family and shed light on how some CBMs and their respective orientation can contribute to substrate preference.



Author(s):  
B. B. Rath ◽  
J. E. O'Neal ◽  
R. J. Lederich

Addition of small amounts of erbium has a profound effect on recrystallization and grain growth in titanium. Erbium, because of its negligible solubility in titanium, precipitates in the titanium matrix as a finely dispersed second phase. The presence of this phase, depending on its average size, distribution, and volume fraction in titanium, strongly inhibits the migration of grain boundaries during recrystallization and grain growth, and thus produces ultimate grains of sub-micrometer dimensions. A systematic investigation has been conducted to study the isothermal grain growth in electrolytically pure titanium and titanium-erbium alloys (Er concentration ranging from 0-0.3 at.%) over the temperature range of 450 to 850°C by electron microscopy.



Author(s):  
A. Strojnik ◽  
J.W. Scholl ◽  
V. Bevc

The electron accelerator, as inserted between the electron source (injector) and the imaging column of the HVEM, is usually a strong lens and should be optimized in order to ensure high brightness over a wide range of accelerating voltages and illuminating conditions. This is especially true in the case of the STEM where the brightness directly determines the highest resolution attainable. In the past, the optical behavior of accelerators was usually determined for a particular configuration. During the development of the accelerator for the Arizona 1 MEV STEM, systematic investigation was made of the major optical properties for a variety of electrode configurations, number of stages N, accelerating voltages, 1 and 10 MEV, and a range of injection voltages ϕ0 = 1, 3, 10, 30, 100, 300 kV).



1989 ◽  
Vol 32 (3) ◽  
pp. 698-702 ◽  
Author(s):  
Daniel Harris ◽  
Donald Fucci ◽  
Linda Petrosino

The present experiment was a preliminary attempt to use the psychophysical scaling methods of magnitude estimation and cross-modal matching to investigate suprathreshold judgments of lingual vibrotactile and auditory sensation magnitudes for 20 normal young adult subjects. A 250-Hz lingual vibrotactile stimulus and a 1000-Hz binaural auditory stimulus were employed. To obtain judgments for nonoral vibrotactile sensory magnitudes, the thenar eminence of the hand was also employed as a test site for 5 additional subjects. Eight stimulus intensities were presented during all experimental tasks. The results showed that the slopes of the log-log vibrotactile magnitude estimation functions decreased at higher stimulus intensity levels for both test sites. Auditory magnitude estimation functions were relatively constant throughout the stimulus range. Cross-modal matching functions for the two stimuli generally agreed with functions predicted from the magnitude estimation data, except when subjects adjusted vibration on the tongue to match auditory stimulus intensities. The results suggested that the methods of magnitude estimation and cross-modal matching may be useful for studying sensory processing in the speech production system. However, systematic investigation of response biases associated with vibrotactile-auditory psychophysical scaling tasks appears to be a prerequisite.



1987 ◽  
Vol 57 (01) ◽  
pp. 017-019 ◽  
Author(s):  
Magda M W Ulrich ◽  
Berry A M Soute ◽  
L Johan M van Haarlem ◽  
Cees Vermeer

SummaryDecarboxylated osteocalcins were prepared and purified from bovine, chicken, human and monkey bones and assayed for their ability to serve as a substrate for vitamin K-dependent carboxylase from bovine liver. Substantial differences were observed, especially between bovine and monkey d-osteocalcin. Since these substrates differ only in their amino acid residues 3 and 4, it seems that these residues play a role in the recognition of a substrate by hepatic carboxylase.



2005 ◽  
Vol 43 (05) ◽  
Author(s):  
O Goetze ◽  
H Fruehauf ◽  
MA Kwiatek ◽  
M Thumshirn ◽  
W Schwizer ◽  
...  


1996 ◽  
Vol 82 (1) ◽  
pp. 147-152 ◽  
Author(s):  
Douglas Vickers ◽  
Charles Pearce

Trail-making tests such as Oswald and Roth's 1987 Zahlen-Verbindungs-Test offer sensitive and reliable indicators of cognitive efficiency that are also simple, inexpensive, and quick to administer. A disadvantage is that there exist only a limited number of test forms so the scope for repeated administration and systematic investigation is restricted. The basic reason is that the principled generation of such pathways remains an unsolved analytical problem. In this note we propose an heuristic stratagem for the generation of alternative test forms for the Zahlen-Verbindungs-Test.



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