2YGW

Crystal structure of human MCD

2YGW の概要

• エントリーDOI: 10.2210/pdb2ygw/pdb
• 分子名称: MALONYL-COA DECARBOXYLASE, MITOCHONDRIAL, UNKNOWN ATOM OR ION, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: lyase
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Cytoplasm : O95822
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 102921.63

構造登録者

Vollmar, M.,Puranik, S.,Krojer, T.,Savitsky, P.,Allerston, C.,Yue, W.W.,Chaikuad, A.,von Delft, F.,Gileadi, O.,Kavanagh, K.,Bountra, C.,Arrowsmith, C.H.,Weigelt, J.,Edwards, A.,Oppermann, U. (登録日: 2011-04-21, 公開日: 2012-02-15, 最終更新日: 2024-10-16)

主引用文献

Froese, D.S.,Forouhar, F.,Tran, T.H.,Vollmar, M.,Kim, Y.S.,Lew, S.,Neely, H.,Seetharaman, J.,Shen, Y.,Xiao, R.,Acton, T.B.,Everett, J.K.,Cannone, G.,Puranik, S.,Savitsky, P.,Krojer, T.,Pilka, E.S.,Kiyani, W.,Lee, W.H.,Marsden, B.D.,von Delft, F.,Allerston, C.K.,Spagnolo, L.,Gileadi, O.,Montelione, G.T.,Oppermann, U.,Yue, W.W.,Tong, L.
Crystal Structures of Malonyl-Coenzyme a Decarboxylase Provide Insights Into its Catalytic Mechanism and Disease-Causing Mutations.
Structure, 21:1182-, 2013

PubMed Abstract: Malonyl-coenzyme A decarboxylase (MCD) is found from bacteria to humans, has important roles in regulating fatty acid metabolism and food intake, and is an attractive target for drug discovery. We report here four crystal structures of MCD from human, Rhodopseudomonas palustris, Agrobacterium vitis, and Cupriavidus metallidurans at up to 2.3 Å resolution. The MCD monomer contains an N-terminal helical domain involved in oligomerization and a C-terminal catalytic domain. The four structures exhibit substantial differences in the organization of the helical domains and, consequently, the oligomeric states and intersubunit interfaces. Unexpectedly, the MCD catalytic domain is structurally homologous to those of the GCN5-related N-acetyltransferase superfamily, especially the curacin A polyketide synthase catalytic module, with a conserved His-Ser/Thr dyad important for catalysis. Our structures, along with mutagenesis and kinetic studies, provide a molecular basis for understanding pathogenic mutations and catalysis, as well as a template for structure-based drug design.

PubMed: 23791943
DOI: 10.1016/J.STR.2013.05.001

実験手法

X-RAY DIFFRACTION (2.8 Å)