6KV3

Crystal Structure of NAD+ Synthetase from Staphylococcus aureus

Summary for 6KV3

• Entry DOI: 10.2210/pdb6kv3/pdb
• Descriptor: NH(3)-dependent NAD(+) synthetase (2 entities in total)
• Functional Keywords: staphylococcus aureus, nad synthetase nucleotide-binding protein, nad pathway, ligase
• Biological source: Staphylococcus aureus (strain COL)
• Total number of polymer chains: 4
• Total formula weight: 127227.84

Authors

Nasrin, S.K.,Sandeep, S.K. (deposition date: 2019-09-03, release date: 2020-09-09, Last modification date: 2023-11-22)

Primary citation

Sultana, K.N.,Kuldeep, J.,Siddiqi, M.I.,Srivastava, S.K.
Crystallographic and molecular dynamics simulation analysis of NAD synthetase from methicillin resistant Staphylococcus aureus (MRSA).
Int.J.Biol.Macromol., 165:2349-2362, 2020

PubMed Abstract: NAD synthetase (NadE) catalyzes the last step in NAD biosynthesis, transforming deamido-NAD into NAD by a two-step reaction with co-substrates ATP and amide donor ammonia. In this study, we report the crystal structure of Staphylococcus aureus NAD synthetase enzyme (saNadE) at 2.3 Å resolution. We used this structure to perform molecular dynamics simulations of apo-enzyme, enzyme-substrate (NadE with ATP and NaAD) and enzyme-intermediate complexes (NadE with NaAD-AMP) to investigate key binding interactions and explore the conformational transitions and flexibility of the binding pocket. Our results show large shift of N-terminal region in substrate bound form which is important for ATP binding. Substrates drive the correlated movement of loop regions surrounding it as well as some regions distal to the active site and stabilize them at complex state. Principal component analysis of atomic projections distinguish feasible trajectories to delineate distinct motions in enzyme-substrate to enzyme-intermediate states. Our results suggest mixed binding involving dominant induced fit and conformational selection. MD simulation extracted ensembles of NadE could potentially be utilized for in silico screening and structure based design of more effective Methicillin Resistant Staphylococcus aureus (MRSA) inhibitors.

PubMed: 33098904
DOI: 10.1016/j.ijbiomac.2020.10.096

Experimental method

X-RAY DIFFRACTION (2.3 Å)