3gui

T4 lysozyme M102E/L99A mutant with buried charge in apolar cavity--Apo structureT4 lysozyme M102E/L99A mutant with buried charge in apolar cavity--Apo structure

Structural highlights 3gui is a 1 chain structure with sequence from Bpt4. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , , , NonStd Res: Related: 3guj, 3guk, 3gul, 3gum, 3gun, 3guo, 3gup Gene: E (BPT4) Activity: Lysozyme, with EC number 3.2.1.17 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [LYS_BPT4] Helps to release the mature phage particles from the cell wall by breaking down the peptidoglycan. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Both large-to-small and non-polar-to-polar mutations in the hydrophobic core of T4 lysozyme cause significant loss in stability. By including supplementary stabilizing mutations we constructed a variant that combines the cavity-creating substitution Leu99 Ala with the buried charge mutant Met102 Glu. Crystal structure determination confirmed that this variant has a large cavity with the side-chain of Glu102 located within the cavity wall. The cavity includes a large disk-shaped region plus a bulge. The disk-like region is essentially non-polar, similar to L99A, while the Glu102 substituent is located in the vicinity of the bulge. Three ordered water molecules bind within this part of the cavity and appear to stabilize the conformation of Glu102. Glu102 has an estimated pKa of about 5.5-6.5, suggesting that it is at least partially charged in the crystal structure. The polar ligands pyridine, phenol and aniline bind within the cavity and crystal structures of the complexes show one or two water molecules to be retained. Non-polar ligands of appropriate shape can also bind in the cavity and in some cases exclude all three water molecules. This disrupts the hydrogen-bond network and causes the Glu102 side-chain to move away from the ligand by up to 0.8 A where it remains buried in a completely non-polar environment. Isothermal titration calorimetry revealed that the binding of these compounds stabilizes the protein by 4 6 kcal/mol. For both polar and non polar ligands the binding is enthalpically driven. Large negative changes in entropy adversely balance the binding of the polar ligands, whereas entropy has little effect on the non polar ligand binding. Use of Stabilizing Mutations to Engineer a Charged Group within a Ligand-binding Hydrophobic Cavity in T4 Lysozyme.,Liu L, Baase WA, Michael M, Matthews BW Biochemistry. 2009 Aug 10. PMID:19663503 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Lysozyme 3D structures

spinqualitylabelsall models 3gui, resolution 1.45Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image