4uc5

Neisseria Meningitidis DAH7PS-Phenylalanine regulatedNeisseria Meningitidis DAH7PS-Phenylalanine regulated

Structural highlights 4uc5 is a 4 chain structure with sequence from Neisseria meningitidis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.19Å Ligands: , , , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q9K169_NEIMB Stereospecific condensation of phosphoenolpyruvate (PEP) and D-erythrose-4-phosphate (E4P) giving rise to 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP) (By similarity).[PIRNR:PIRNR001361] Publication Abstract from PubMed Allosteric regulation of protein function, the process by which binding of an effector molecule provokes a functional response from a distal site, is critical for metabolic pathways. Yet, the way the allosteric signal is communicated remains elusive, especially in dynamic, entropically-driven regulation mechanisms for which no major conformational changes are observed. To identify these dynamic allosteric communication networks, we have developed an approach that monitors the pKa variations of ionizable residues over the course of molecular dynamics simulations performed in the presence and absence of an allosteric regulator. As the pKa of ionizable residues depends on their environment, it represents a simple metric to monitor changes in several complex factors induced by binding an allosteric effector. These factors include coulombic interactions, hydrogen bounding and solvation, as well as backbone motions and sidechain fluctuations. The predictions that can be made with this method concerning the roles of ionizable residues for allosteric communication can then be easily tested experimentally by changing the working pH of the protein or performing single point mutations. To demonstrate the method's validity, we have applied this approach to the subtle dynamic regulation mechanism observed for Neisseria meningitidis 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase, the first enzyme of aromatic biosynthesis. We were able to identify key communication pathways linking the allosteric binding site to the active site of the enzyme and to validate these findings experimentally by reestablishing the catalytic activity of allosterically inhibited enzyme via modulation of the working pH, without compromising the binding affinity of the allosteric regulator. Calculated pKa variations expose dynamic allosteric communication networks.,Lang EJ, Heyes LC, Jameson GB, Parker EJ J Am Chem Soc. 2016 Jan 21. PMID:26794122 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also DAHP synthase 3D structures

spinqualitylabelsall models 4uc5, resolution 2.19Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image