3S1W

Transaldolase variant Lys86Ala from Thermoplasma acidophilum in complex with glycerol and citrate

Summary for 3S1W

• Entry DOI: 10.2210/pdb3s1w/pdb
• Related: 3S0C 3S1U 3S1V 3S1X
• Descriptor: Probable transaldolase, GLYCEROL, CITRATE ANION, ... (4 entities in total)
• Functional Keywords: alpha-beta barrel, domain swapping, protein dynamics, conformational selection, transferase
• Biological source: Thermoplasma acidophilum
• Total number of polymer chains: 5
• Total formula weight: 123588.17

Authors

Lehwess-Litzmann, A.,Neumann, P.,Parthier, C.,Tittmann, K. (deposition date: 2011-05-16, release date: 2011-08-24, Last modification date: 2023-09-13)

Primary citation

Lehwess-Litzmann, A.,Neumann, P.,Parthier, C.,Ludtke, S.,Golbik, R.,Ficner, R.,Tittmann, K.
Twisted Schiff base intermediates and substrate locale revise transaldolase mechanism.
Nat.Chem.Biol., 7:678-684, 2011

PubMed Abstract: We examined the catalytic cycle of transaldolase (TAL) from Thermoplasma acidophilum by cryocrystallography and were able to structurally characterize--for the first time, to our knowledge--different genuine TAL reaction intermediates. These include the Schiff base adducts formed between the catalytic lysine and the donor ketose substrates fructose-6-phosphate and sedoheptulose-7-phosphate as well as the Michaelis complex with acceptor aldose erythrose-4-phosphate. These structural snapshots necessitate a revision of the accepted reaction mechanism with respect to functional roles of active site residues, and they further reveal fundamental insights into the general structural features of enzymatic Schiff base intermediates and the role of conformational dynamics in enzyme catalysis, substrate binding and discrimination. A nonplanar arrangement of the substituents around the Schiff base double bond was observed, suggesting that a structurally encoded reactant-state destabilization is a driving force of catalysis. Protein dynamics and the intrinsic hydrogen-bonding pattern appear to be crucial for selective recognition and binding of ketose as first substrate.

PubMed: 21857661
DOI: 10.1038/nchembio.633

Experimental method

X-RAY DIFFRACTION (1.8 Å)