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DNA glycosylase MutY plays a critical role in suppression of mutations resulted from oxidative damage, as highlighted by cancer-association of the human enzyme. MutY requires a highly conserved catalytic Asp residue for excision of adenines misinserted opposite 8-oxo-7,8-dihydroguanine (OG). A nearby Asn residue hydrogen bonds to the catalytic Asp in structures of MutY and its mutation to Ser is an inherited variant in human MUTYH associated with colorectal cancer. We captured structural snapshots of N146S Geobacillus stearothermophilus MutY bound to DNA containing a substrate, a transition state analog and enzyme-catalyzed abasic site products to provide insight into the base excision mechanism of MutY and the role of Asn. Surprisingly, despite the ability of N146S to excise adenine and purine (P) in vitro, albeit at slow rates, N146S-OG:P complex showed a calcium coordinated to the purine base altering its conformation to inhibit hydrolysis. We obtained crystal structures of N146S Gs MutY bound to its abasic site product by removing the calcium from crystals of N146S-OG:P complex to initiate catalysis in crystallo or by crystallization in the absence of calcium. The product structures of N146S feature enzyme-generated β-anomer abasic sites that support a retaining mechanism for MutY-catalyzed base excision.

 

Distance compression, which refers to the underestimation of ego-centric distance to objects, is a common problem in immersive virtual environments. Besides visually compensating the compressed distance, several studies have shown that auditory information can be an alternative solution for this problem. In particular, reverberation time (RT) has been proven to be an effective method to compensate distance compression. To further explore the feasibility of applying audio information to improve distance perception, we investigate whether users’ egocentric distance perception can be calibrated, and whether the calibrated effect can be carried over and even sustain for a longer duration. We conducted a study to understand the perceptual learning and carryover effects by using RT as stimuli for users to perceive distance in IVEs. The results show that the carryover effect exists after calibration, which indicates people can learn to perceive distances by attuning reverberation time, and the accuracy even remains a constant level after 6 months. Our findings could potentially be utilized to improve the distance perception in VR systems as the calibration of auditory distance perception in VR could sustain for several months. This could eventually avoid the burden of frequent training regimens.