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Vagococcus lutrae kaynaklı L-alanine dehydrogenase: yapısal analizi ve endüstriyel potensiyeli

2025
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Advisor: Dr. Öğr. Üyesi Hasan Demirci ; Dr. Öğr. Üyesi Onur Öztaş ; Doç. Dr. Özge Şensoy

Abstract (EN)

L-Alanine dehydrogenase from Vagococcus lutrae (VlAlaDH) catalyzes the reversible oxidation-reduction reaction between L-alanine and pyruvate. The enzyme's ability to generate a valuable product in a single enzymatic step has increased interest in bacterial AlaDHs. In this study, a novel wild-type apo structure of AlaDH from under characterized organism is presented which could serve as a candidate for L-alanine production with minimal pyruvate byproduct. The discovery lays the groundwork for future studies for protein engineering has been laid. The structure was determined using highly complex experimental methodology of X- ray crystallography with the "Turkish Delight" diffractometer in the ambient temperature in near neutral pH. This approach enabled the determination of the apo-structure of VlAlaDH at 3.2 Å resolution revealing a homo-hexamer oligomerization with conserved Rossmann fold motifs. The main takeaway from the study was the enzyme retained the key motif architecture observed in each homolog structure. The retained motifs being one NAD+ -binding Rossmann fold connected with conserved 𝛼-helices linker to a second Rossmann fold which carried the catalytic residues for pyruvate and L-alanine. Notable differences were observed in the NAD+-binding Rossmann fold where it carried some similarities in residue level to a thermostable bacterial AlaDHs called Geobacillus kaustophilus and Thermus thermophilus. Specifically, residue 270 substituted from Asp to Gln, residue 240 also showed change from Val to Ile between Geobacillus kaustophilus, and between Thermus thermophilus and Vagococcus lutrae both carrying Ile at the residue number 198 but not the homologs. These residues participate in NAD+ binding into the cleft through hydrogen bonds and hydrophobic interactions. As the primary binding substrate being NAD+, these substitutions may be targeted for future studies. The phylogenetic tree further supports that even the evolutionary distance of the species shared common adaptations at coenzymelevel.

Author

Dr. Cengiz Kaan Ferah

How to Cite

Cengiz Kaan Ferah (Master Thesis). Vagococcus lutrae kaynaklı L-alanine dehydrogenase: yapısal analizi ve endüstriyel potensiyeli, 2025, Koç University.

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