title: Structural insight for substrate tolerance to 2-deoxyribose-5-phosphate aldolase from the pathogen Streptococcus suis.
abstract: 2-deoxyribose-5-phosphate aldolase (DERA) is a class I aldolase that catalyzes aldol condensation of two aldehydes in the active site, which is particularly germane in drug manufacture. Structural and biochemical studies have shown that the active site of DERA is typically loosely packed and displays broader substrate specificity despite sharing conserved folding architecture with other aldolases. The most distinctive structural feature of DERA compared to other aldolases is short and flexible C-terminal region. This region is also responsible for substrate recognition. Therefore, substrate tolerance may be related to the C-terminal structural features of DERA. Here, we determined the crystal structures of full length and C-terminal truncated DERA from Streptococcus suis (SsDERA). In common, both contained the typical (α/β)8 TIM-barrel fold of class I aldolases. Surprisingly, C-terminal truncation resulting in missing the last α9 and β8 secondary elements, allowed DERA to maintain activity comparable to the fulllength enzyme. Specifically, Arg186 and Ser205 residues at the C-terminus appeared mutually supplemental or less indispensible for substrate phosphate moiety recognition. Our results suggest that DERA might adopt a shorter C-terminal region than conventional aldolases during evolution pathway, resulting in a broader range of substrate tolerance through active site flexibility.
authors.affiliation: Department of Cellular and Molecular Medicine, Chosun University School of Medicine, Gwangju, 501-759, Republic of Korea.|National Research Center for Dementia, Chosun University, Gwangju, 61452, Republic of Korea.
authors.forename: Thinh-Phat
authors.initials: TP
authors.lastname: Cao
authors.affiliation: Jeonbuk Branch Institute, Korea Research Institute of Bioscience and Biotechnology, Jeongeup, 580-185, Republic of Korea.
authors.forename: Joong-Su
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Jeonbuk Branch Institute, Korea Research Institute of Bioscience and Biotechnology, Jeongeup, 580-185, Republic of Korea.
authors.forename: Mi-Hee
authors.initials: MH
authors.lastname: Woo
authors.affiliation: Department of Cellular and Molecular Medicine, Chosun University School of Medicine, Gwangju, 501-759, Republic of Korea.|School of Life Sciences and Silver Health Bio Research Center, Gwangju Institute of Science and Technology, Gwangju, 61005, Republic of Korea.
authors.forename: Jin Myung
authors.initials: JM
authors.lastname: Choi
authors.affiliation: School of Life Sciences and Silver Health Bio Research Center, Gwangju Institute of Science and Technology, Gwangju, 61005, Republic of Korea.|School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, 61005, Republic of Korea.
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Jun
authors.affiliation: National Research Center for Dementia, Chosun University, Gwangju, 61452, Republic of Korea.|Department of Biomedical Science, Chosun University, Gwangju, 61452, Republic of Korea.
authors.forename: Kun Ho
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Cellular and Molecular Medicine, Chosun University School of Medicine, Gwangju, 501-759, Republic of Korea. sunglee@chosun.ac.kr.
authors.forename: Sung Haeng
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000446:Aldehyde-Lyases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012267:Ribosemonophosphates / Q000378:metabolism; D017011:Streptococcus suis / Q000201:enzymology* / Q000235:genetics; D013379:Substrate Specificity
chemical_list: D021122:Protein Subunits; D011994:Recombinant Proteins; D012267:Ribosemonophosphates; C058245:2-deoxyribose 5-phosphate; D000446:Aldehyde-Lyases; C020019:deoxyribose-phosphate aldolase
keywords: 2-deoxyribose-5-phosphate aldolase; Class I aldolase; DERA; S. suis; TIM-barrel