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Crystal structure of mitochondrial alcohol dehydrogenase isozyme III from Komagataella phaffii GS115
Structural highlights
FunctionPublication Abstract from PubMedBACKGROUND: Alcohol dehydrogenases (ADHs) catalyze the reversible oxidation of alcohol using NAD(+) or NADP(+) as cofactor. Three ADH homologues have been identified in Komagataella phaffii GS115 (also named Pichia pastoris GS115), ADH1, ADH2 and ADH3, among which adh3 is the only gene responsible for consumption of ethanol in Komagataella phaffii GS115. However, the relationship between structure and function of mitochondrial alcohol dehydrogenase isozyme III from Komagataella phaffii GS115 (KpADH3) is still not clear yet. METHODS: KpADH3 was purified, identified and characterized by multiple biophysical techniques (Nano LC-MS/MS, Enzymatic activity assay, X-ray crystallography). RESULTS: The crystal structure of KpADH3, which was the first ADH structure from Komagataella phaffii GS115, was solved at 1.745A resolution. Structural analysis indicated that KpADH3 was the sole dimeric ADH structure with face-to-face orientation quaternary structure from yeast. The major structural different conformations located on residues 100-114 (the structural zinc binding loop) and residues 337-344 (the loop between alpha12 and beta15 which covered the catalytic domain). In addition, three channels were observed in KpADH3 crystal structure, channel 2 and channel 3 may be essential for substrate specific recognition, ingress and egress, channel 1 may be the pass-through for cofactor. CONCLUSIONS: KpADH3 plays an important role in the metabolism of alcohols in Komagataella phaffii GS115, and its crystal structure is the only dimeric medium-chain ADH from yeast described so far. GENERAL SIGNIFICANCE: Knowledge of the relationship between structure and function of KpADH3 is crucial for understanding the role of KpADH3 in Komagataella phaffii GS115 mitochondrial metabolism. Investigation of structure and function of mitochondrial alcohol dehydrogenase isozyme III from Komagataella phaffii GS115.,Zhang H, Li Q, Wang L, Chen Y Biochim Biophys Acta. 2018 Feb 21;1862(5):1199-1208. doi:, 10.1016/j.bbagen.2018.02.012. PMID:29474823[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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