8F8O

Crystal Structure of the Succinyl-diaminopimelate Desuccinylase (DapE) from Acinetobacter baumannii in complex with Succinic and L-Lactic Acids

Summary for 8F8O

• Entry DOI: 10.2210/pdb8f8o/pdb
• Descriptor: Succinyl-diaminopimelate desuccinylase, ZINC ION, SUCCINIC ACID, ... (8 entities in total)
• Functional Keywords: center for structural biology of infectious diseases (csbid), dape, succinate, l-lactate, structural genomics, center for structural genomics of infectious diseases, csgid, hydrolase
• Biological source: Acinetobacter baumannii ATCC 17978
• Total number of polymer chains: 2
• Total formula weight: 85741.69

Authors

Minasov, G.,Shuvalova, L.,Brunzelle, J.S.,Dubrovska, I.,Pshenychnyi, S.,Satchell, K.J.F.,Center for Structural Biology of Infectious Diseases (CSBID),Center for Structural Genomics of Infectious Diseases (CSGID) (deposition date: 2022-11-22, release date: 2022-11-30, Last modification date: 2025-09-24)

Primary citation

Kelley, E.H.,Minasov, G.,Konczak, K.,Shuvalova, L.,Brunzelle, J.S.,Shukla, S.,Beulke, M.,Thabthimthong, T.,Olsen, K.W.,Inniss, N.L.,Satchell, K.J.F.,Becker, D.P.
Biochemical and Structural Analysis of the Bacterial Enzyme Succinyl-Diaminopimelate Desuccinylase (DapE) from Acinetobacter baumannii.
Acs Omega, 9:3905-3915, 2024

PubMed Abstract: There is an urgent need for new antibiotics given the rise of antibiotic resistance, and succinyl-diaminopimelate desuccinylase (DapE, E.C. 3.5.1.18) has emerged as a promising bacterial enzyme target. DapE from (DapE) has been studied and inhibitors identified, but it is essential to explore DapE from different species to assess selective versus broad-spectrum therapeutics. We have determined the structure of DapE from the ESKAPE pathogen (DapE) and studied inhibition by known inhibitors of DapE. DapE is inhibited by captopril and sulfate comparable to DapE, but DapE was not significantly inhibited by a known indoline sulfonamide DapE inhibitor. Captopril and sulfate both stabilize DapE by increasing the thermal melting temperature () in thermal shift assays. By contrast, sulfate decreases the stability of the DapE enzyme, whereas captopril increases the stability. Further, we report two crystal structures of selenomethionine-substituted DapE in the closed conformation, one with DapE in complex with succinate derived from enzymatic hydrolysis of -methyl-l,l-SDAP substrate and acetate (PDB code 7T1Q, 2.25 Å resolution), and a crystal structure of DapE with bound succinate along with l-(S)-lactate, a product of degradation of citric acid from the crystallization buffer during X-ray irradiation (PDB code 8F8O, 2.10 Å resolution).

PubMed: 38284080
DOI: 10.1021/acsomega.3c08231

Experimental method

X-RAY DIFFRACTION (2.1 Å)