9JHZ

3-Hydroxybutyryl-CoA dehydrogenase mutant(S117A) with acetoacetyl CoA and NAD

9JHZ の概要

• エントリーDOI: 10.2210/pdb9jhz/pdb
• 分子名称: 3-hydroxyacyl-CoA dehydrogenase, NAD binding domain protein, ACETOACETYL-COENZYME A, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (4 entities in total)
• 機能のキーワード: complex with acetoacetyl coa and nad, oxidoreductase
• 由来する生物種: Faecalibacterium duncaniae (strain DSM 17677 / JCM 31915 / A2-165)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 95119.49

構造登録者

Yang, J.W.,Jeon, H.J.,Park, S.H.,Kim, S.H.,Hwang, K.Y. (登録日: 2024-09-10, 公開日: 2024-11-13)

主引用文献

Yang, J.,Jeon, H.J.,Park, S.,Park, J.,Jang, S.,Shin, B.,Bang, K.,Hawkes, H.K.,Park, S.,Kim, S.,Hwang, K.Y.
Structural Insights and Catalytic Mechanism of 3-Hydroxybutyryl-CoA Dehydrogenase from Faecalibacterium Prausnitzii A2-165.
Int J Mol Sci, 25:-, 2024

PubMed Abstract: Atopic dermatitis (AD) is characterized by a T-helper cell type 2 (Th2) inflammatory response leading to skin damage with erythema and edema. Comparative fecal sample analysis has uncovered a strong correlation between AD and strain A2-165, specifically associated with butyrate production. Therefore, understanding the functional mechanisms of crucial enzymes in the butyrate pathway, such as 3-hydroxybutyryl-CoA dehydrogenase of A2-165 (A2HBD), is imperative. Here, we have successfully elucidated the three-dimensional structure of A2HBD in complex with acetoacetyl-CoA and NAD at a resolution of 2.2Å using the PAL-11C beamline (third generation). Additionally, X-ray data of A2HBD in complex with acetoacetyl-CoA at a resolution of 1.9 Å were collected at PAL-XFEL (fourth generation) utilizing Serial Femtosecond Crystallography (SFX). The monomeric structure of A2HBD consists of two domains, N-terminal and C-terminal, with cofactor binding occurring at the N-terminal domain, while the C-terminal domain facilitates dimerization. Our findings elucidate the binding mode of NAD to A2HBD. Upon acetoacetyl-CoA binding, the crystal structure revealed a significant conformational change in the Clamp-roof domain (root-mean-square deviation of 2.202 Å). Notably, residue R143 plays a critical role in capturing the adenine phosphate ring, underlining its significance in substrate recognition and catalytic activity. The binding mode of acetoacetyl-CoA was also clarified, indicating its lower stability compared to NAD. Furthermore, the conformational change of hydrophobic residues near the catalytic cavity upon substrate binding resulted in cavity shrinkage from an open to closed conformation. This study confirms the conformational changes of catalytic triads involved in the catalytic reaction and presents a proposed mechanism for substrate reduction based on structural observations.

PubMed: 39409040
DOI: 10.3390/ijms251910711

実験手法

X-RAY DIFFRACTION (2.2 Å)