4DI6
crystal structure of nucleoside-diphosphate kinase from Borrelia burgdorferi
Summary for 4DI6
| Entry DOI | 10.2210/pdb4di6/pdb |
| Descriptor | Nucleoside diphosphate kinase (2 entities in total) |
| Functional Keywords | ssgcid, nucleoside diphosphate kinase, kinase, structural genomics, seattle structural genomics center for infectious disease, niaid, national institute of allergy and infectious diseases, transferase |
| Biological source | Borrelia burgdorferi (Lyme disease spirochete) |
| Total number of polymer chains | 6 |
| Total formula weight | 130163.60 |
| Authors | Seattle Structural Genomics Center for Infectious Disease (SSGCID) (deposition date: 2012-01-30, release date: 2012-02-08, Last modification date: 2024-11-27) |
| Primary citation | Dumais, M.,Davies, D.R.,Lin, T.,Staker, B.L.,Myler, P.J.,Van Voorhis, W.C. Structure and analysis of nucleoside diphosphate kinase from Borrelia burgdorferi prepared in a transition-state complex with ADP and vanadate moieties. Acta Crystallogr F Struct Biol Commun, 74:373-384, 2018 Cited by PubMed Abstract: Nucleoside diphosphate kinases (NDKs) are implicated in a wide variety of cellular functions owing to their enzymatic conversion of NDP to NTP. NDK from Borrelia burgdorferi (BbNDK) was selected for functional and structural analysis to determine whether its activity is required for infection and to assess its potential for therapeutic inhibition. The Seattle Structural Genomics Center for Infectious Diseases (SSGCID) expressed recombinant BbNDK protein. The protein was crystallized and structures were solved of both the apoenzyme and a liganded form with ADP and vanadate ligands. This provided two structures and allowed the elucidation of changes between the apo and ligand-bound enzymes. Infectivity studies with ndk transposon mutants demonstrated that NDK function was important for establishing a robust infection in mice, and provided a rationale for therapeutic targeting of BbNDK. The protein structure was compared with other NDK structures found in the Protein Data Bank and was found to have similar primary, secondary, tertiary and quaternary structures, with conserved residues acting as the catalytic pocket, primarily using His132 as the phosphohistidine-transfer residue. Vanadate and ADP complexes model the transition state of this phosphoryl-transfer reaction, demonstrating that the pocket closes when bound to ADP, while allowing the addition or removal of a γ-phosphate. This analysis provides a framework for the design of potential therapeutics targeting BbNDK inhibition. PubMed: 29870023DOI: 10.1107/S2053230X18007392 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
Download full validation report
