1D1G

DIHYDROFOLATE REDUCTASE FROM THERMOTOGA MARITIMA

1D1G の概要

• エントリーDOI: 10.2210/pdb1d1g/pdb
• 関連するPDBエントリー: 1CZ3
• 分子名称: DIHYDROFOLATE REDUCTASE, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, METHOTREXATE, ... (4 entities in total)
• 機能のキーワード: dimer, hyperthermophile, oxidoreductase
• 由来する生物種: Thermotoga maritima
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 40926.30

構造登録者

Dams, T.,Auerbach, G.,Bader, G.,Ploom, T.,Huber, R.,Jaenicke, R. (登録日: 1999-09-16, 公開日: 2000-03-31, 最終更新日: 2024-02-07)

主引用文献

Dams, T.,Auerbach, G.,Bader, G.,Jacob, U.,Ploom, T.,Huber, R.,Jaenicke, R.
The crystal structure of dihydrofolate reductase from Thermotoga maritima: molecular features of thermostability.
J.Mol.Biol., 297:659-672, 2000

PubMed Abstract: Two high-resolution structures have been obtained for dihydrofolate reductase from the hyperthermophilic bacterium Thermotoga maritima in its unliganded state, and in its ternary complex with the cofactor NADPH and the inhibitor, methotrexate. While the overall fold of the hyperthermophilic enzyme is closely similar to monomeric mesophilic dihydrofolate reductase molecules, its quaternary structure is exceptional, in that T. maritima dihydrofolate reductase forms a highly stable homodimer. Here, the molecular reasons for the high intrinsic stability of the enzyme are elaborated and put in context with the available data on the physical parameters governing the folding reaction. The molecule is extremely rigid, even with respect to structural changes during substrate binding and turnover. Subunit cooperativity can be excluded from structural and biochemical data. Major contributions to the high intrinsic stability of the enzyme result from the formation of the dimer. Within the monomer, only subtle stabilizing interactions are detectable, without clear evidence for any of the typical increments of thermal stabilization commonly reported for hyperthermophilic proteins. The docking of the subunits is optimized with respect to high packing density in the dimer interface, additional salt-bridges and beta-sheets. The enzyme does not show significant structural changes upon binding its coenzyme, NADPH, and the inhibitor, methotrexate. The active-site loop, which is known to play an important role in catalysis in mesophilic dihydrofolate reductase molecules, is rearranged, participating in the association of the subunits; it no longer participates in catalysis.

PubMed: 10731419
DOI: 10.1006/jmbi.2000.3570

実験手法

X-RAY DIFFRACTION (2.1 Å)