5v7e

T4 lysozyme Y18Ymcl

spinqualitylabelsall models 5v7e, resolution 1.36Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5v7e 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: HED, NA NonStd Res: 3CT Related: 5v7d, 5v7f Gene: e, T4Tp126 (BPT4) Activity: Lysozyme, with EC number 3.2.1.17 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The construction of more stable proteins is important in biomolecular engineering, particularly in the design of biologics-based therapeutics. We show here that replacing the tyrosine at position 18 (Y18) of T4 lysozyme with the unnatural amino acid m-chlorotyrosine ( (mCl)Y) increases both the thermal stability (increasing the melting temperature by approximately 1 degrees C and the melting enthalpy by 3 kcal/mol) and the enzymatic activity at elevated temperatures (15% higher than that of the parent enzyme at 40 degrees C) of this classic enzyme. The chlorine of (mCl)Y forms a halogen bond (XB) to the carbonyl oxygen of the peptide bond at glycine 28 (G28) in a tight loop near the active site. In this case, the XB potential of the typically weak XB donor Cl is shown from quantum chemical calculations to be significantly enhanced by polarization via an intramolecular hydrogen bond (HB) from the adjacent hydroxyl substituent of the tyrosyl side chain, resulting in a distinctive synergistic HB-enhanced XB (or HeX-B for short) interaction. The larger halogens (bromine and iodine) are not well accommodated within this same loop and, consequently, do not exhibit the effects on protein stability or function associated with the HeX-B interaction. Thus, we have for the first time demonstrated that an XB can be engineered to stabilize and increase the activity of an enzyme, with the increased stabilizing potential of the HeX-B further extending the application of halogenated amino acids in the design of more stable protein therapeutics. Increasing Enzyme Stability and Activity through Hydrogen Bond-Enhanced Halogen Bonds.,Carlsson AC, Scholfield MR, Rowe RK, Ford MC, Alexander AT, Mehl RA, Ho PS Biochemistry. 2018 Jul 3. doi: 10.1021/acs.biochem.8b00603. PMID:29921126 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Lysozyme 3D structures

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