4KXX

Human transketolase in covalent complex with donor ketose D-sedoheptulose-7-phosphate

Summary for 4KXX

• Entry DOI: 10.2210/pdb4kxx/pdb
• Descriptor: Transketolase, (2R,3R,4S,5R,6S)-2,3,4,5,6,7-hexahydroxyheptyl dihydrogen phosphate, THIAMINE DIPHOSPHATE, ... (7 entities in total)
• Functional Keywords: thiamin diphosphate, enzyme catalysis, pentose phosphate pathway, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 71157.06

Authors

Neumann, P.,Luedtke, S.,Ficner, R.,Tittmann, K. (deposition date: 2013-05-28, release date: 2013-08-21, Last modification date: 2023-09-20)

Primary citation

Ludtke, S.,Neumann, P.,Erixon, K.M.,Leeper, F.,Kluger, R.,Ficner, R.,Tittmann, K.
Sub-angstrom-resolution crystallography reveals physical distortions that enhance reactivity of a covalent enzymatic intermediate.
Nat Chem, 5:762-767, 2013

PubMed Abstract: It is recognized widely that enzymes promote reactions by providing a pathway that proceeds through a transition state of lower energy. In principle, further rate enhancements could be achieved if intermediates are prevented from relaxing to their lowest energy state, and thereby reduce the barrier to the subsequent transition state. Here, we report sub-ångström-resolution crystal structures of genuine covalent reaction intermediates of transketolase. These structures reveal a pronounced out-of-plane distortion of over 20° for the covalent bond that links cofactor and substrate, and a specific elongation of the scissile substrate carbon-carbon bond (d > 1.6 Å). To achieve these distortions, the protein's conformation appears to prevent relaxation of a substrate-cofactor intermediate. The results implicate a reduced barrier to the subsequent step that is consistent with an intermediate of raised energy and leads to a more efficient overall process.

PubMed: 23965678
DOI: 10.1038/nchem.1728

Experimental method

X-RAY DIFFRACTION (1.03 Å)