8ADQ

Crystal structure of holo-SwHPA-Mg (hydroxy ketone aldolase) from Sphingomonas wittichii RW1 in complex with hydroxypyruvate and D-Glyceraldehyde

Summary for 8ADQ

• Entry DOI: 10.2210/pdb8adq/pdb
• Descriptor: HpcH/HpaI aldolase, 3-HYDROXYPYRUVIC ACID, D-Glyceraldehyde, ... (8 entities in total)
• Functional Keywords: hydroxy-keto aldolase; aldol condensation; aldol cleavage; stereospecificity; tim barrel fold, lyase
• Biological source: Rhizorhabdus wittichii RW1
• Total number of polymer chains: 1
• Total formula weight: 28586.24

Authors

Justo, I.,Marsden, S.R.,Hanefeld, U.,Bento, I. (deposition date: 2022-07-11, release date: 2022-11-23, Last modification date: 2024-01-31)

Primary citation

Marsden, S.R.,Wijma, H.J.,Mohr, M.K.F.,Justo, I.,Hagedoorn, P.L.,Laustsen, J.,Jeffries, C.M.,Svergun, D.,Mestrom, L.,McMillan, D.G.G.,Bento, I.,Hanefeld, U.
Substrate Induced Movement of the Metal Cofactor between Active and Resting State.
Angew.Chem.Int.Ed.Engl., 61:e202213338-e202213338, 2022

PubMed Abstract: Regulation of enzyme activity is vital for living organisms. In metalloenzymes, far-reaching rearrangements of the protein scaffold are generally required to tune the metal cofactor's properties by allosteric regulation. Here structural analysis of hydroxyketoacid aldolase from Sphingomonas wittichii RW1 (SwHKA) revealed a dynamic movement of the metal cofactor between two coordination spheres without protein scaffold rearrangements. In its resting state configuration (M ), the metal constitutes an integral part of the dimer interface within the overall hexameric assembly, but sterical constraints do not allow for substrate binding. Conversely, a second coordination sphere constitutes the catalytically active state (M ) at 2.4 Å distance. Bidentate coordination of a ketoacid substrate to M affords the overall lowest energy complex, which drives the transition from M to M . While not described earlier, this type of regulation may be widespread and largely overlooked due to low occupancy of some of its states in protein crystal structures.

PubMed: 36214476
DOI: 10.1002/anie.202213338

Experimental method

X-RAY DIFFRACTION (1.6 Å)