2C6Q

Crystal structure of human guanosine monophosphate reductase 2 GMPR2 in complex with IMP and NADPH

2C6Q の概要

• エントリーDOI: 10.2210/pdb2c6q/pdb
• 関連するPDBエントリー: 2BZN
• 分子名称: GMP REDUCTASE 2, INOSINIC ACID, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (4 entities in total)
• 機能のキーワード: tim barrel, metal-binding, nadp, oxidoreductase, potassium
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 313263.94

構造登録者

Kursula, P.,Stenmark, P.,Arrowsmith, C.,Berglund, H.,Edwards, A.,Ehn, M.,Graslund, S.,Hammarstrom, M.,Hallberg, B.M.,Kotenyova, T.,Nilsson-Ehle, P.,Ogg, D.,Persson, C.,Sagemark, J.,Schuler, H.,Sundstrom, M.,Thorsell, A.,Weigelt, J.,Nordlund, P. (登録日: 2005-11-11, 公開日: 2005-11-30, 最終更新日: 2024-10-23)

主引用文献

Patton, G.C.,Stenmark, P.,Gollapalli, D.R.,Sevastik, R.,Kursula, P.,Flodin, S.,Schuler, H.,Swales, C.T.,Eklund, H.,Himo, F.,Nordlund, P.,Hedstrom, L.
Cofactor Mobility Determines Reaction Outcome in the Impdh and Gmpr (Beta-Alpha)(8) Barrel Enzymes.
Nat.Chem.Biol., 7:950-, 2011

PubMed Abstract: Inosine monophosphate dehydrogenase (IMPDH) and guanosine monophosphate reductase (GMPR) belong to the same structural family, share a common set of catalytic residues and bind the same ligands. The structural and mechanistic features that determine reaction outcome in the IMPDH and GMPR family have not been identified. Here we show that the GMPR reaction uses the same intermediate E-XMP* as IMPDH, but in this reaction the intermediate reacts with ammonia instead of water. A single crystal structure of human GMPR type 2 with IMP and NADPH fortuitously captures three different states, each of which mimics a distinct step in the catalytic cycle of GMPR. The cofactor is found in two conformations: an 'in' conformation poised for hydride transfer and an 'out' conformation in which the cofactor is 6 Å from IMP. Mutagenesis along with substrate and cofactor analog experiments demonstrate that the out conformation is required for the deamination of GMP. Remarkably, the cofactor is part of the catalytic machinery that activates ammonia.

PubMed: 22037469
DOI: 10.1038/NCHEMBIO.693

実験手法

X-RAY DIFFRACTION (1.7 Å)