FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2044098466> ?p ?o ?g. }

• W2044098466 endingPage "2968" @default.
• W2044098466 startingPage "2946" @default.
• W2044098466 abstract "Antibodies HyHEL8, HyHEL10, and HyHEL26 (HH8, HH10, and HH26, respectively) recognize highly overlapping epitopes on hen egg-white lysozyme (HEL) with similar affinities, but with different specificities. HH8 binding to HEL is least sensitive toward mutations in the epitope and thus is most cross-reactive, HH26 is most sensitive, whereas the sensitivity of HH10 lies in between HH8 and HH26. Here we have investigated intra- and intermolecular interactions in three antibody-protein complexes: theoretical models of HH8-HEL and HH26-HEL complexes, and the x-ray crystal structure of HH10-HEL complex. Our results show that HH8-HEL has the lowest number and HH26-HEL has the highest number of intra- and intermolecular hydrogen bonds. The number of salt bridges is lowest in HH8-HEL and highest in HH26-HEL. The binding site salt bridges in HH8-HEL are not networked, and are weak, whereas, in HH26-HEL, an intramolecular salt-bridge triad at the binding site is networked to an intermolecular triad to form a pentad. The pentad and each salt bridge of this pentad are exceptionally stabilizing. The number of binding-site salt bridges and their strengths are intermediate in HH10-HEL, with an intramolecular triad. Our further calculations show that the electrostatic component contributes the most to binding energy of HH26-HEL, whereas the hydrophobic component contributes the most in the case of HH8-HEL. A hot-spot epitope residue Lys-97 forms an intermolecular salt bridge in HH8-HEL, and participates in the intermolecular pentad in the HH26-HEL complex. Mutant modeling and surface plasmon resonance (SPR) studies show that this hot-spot epitope residue contributes significantly more to the binding than an adjacent epitope residue, Lys-96, which does not form a salt bridge in any of the three HH-HEL complexes. Furthermore, the effect of mutating Lys-97 is most severe in HH26-HEL. Lys-96, being a charged residue, also contributes the most in HH26-HEL among the three complexes. The SPR results on these mutants also highlight that the apparent electrostatic steering on net on rates actually act at post-collision level stabilization of the complex. The significance of this work is the observed variations in electrostatic interactions among the three complexes. Our work demonstrates that higher electrostatics, both as a number of short-range electrostatic interactions and their contributions, leads to higher binding specificity. Strong salt bridges, their networking, and electrostatically driven binding, limit flexibilities through geometric constrains. In contrast, hydrophobic driven binding and low levels of electrostatic interactions are associated with conformational flexibility and cross-reactivity." @default.
• W2044098466 created "2016-06-24" @default.
• W2044098466 creator A5010864763 @default.
• W2044098466 creator A5029277387 @default.
• W2044098466 creator A5048859030 @default.
• W2044098466 creator A5064146416 @default.
• W2044098466 date "2002-12-01" @default.
• W2044098466 modified "2023-10-16" @default.
• W2044098466 title "Differences in Electrostatic Properties at Antibody–Antigen Binding Sites: Implications for Specificity and Cross-Reactivity" @default.
• W2044098466 cites W122050955 @default.
• W2044098466 cites W1489338305 @default.
• W2044098466 cites W1501561646 @default.
• W2044098466 cites W1523633230 @default.
• W2044098466 cites W1538857361 @default.
• W2044098466 cites W1539803228 @default.
• W2044098466 cites W1548718817 @default.
• W2044098466 cites W1573221685 @default.
• W2044098466 cites W1965127482 @default.
• W2044098466 cites W1966041739 @default.
• W2044098466 cites W1968702502 @default.
• W2044098466 cites W1970197953 @default.
• W2044098466 cites W1975142943 @default.
• W2044098466 cites W1976981353 @default.
• W2044098466 cites W1977829473 @default.
• W2044098466 cites W1979234818 @default.
• W2044098466 cites W1980022131 @default.
• W2044098466 cites W1984508840 @default.
• W2044098466 cites W1985563220 @default.
• W2044098466 cites W1991410475 @default.
• W2044098466 cites W1992743196 @default.
• W2044098466 cites W1995269926 @default.
• W2044098466 cites W1995380127 @default.
• W2044098466 cites W1997870466 @default.
• W2044098466 cites W1999271199 @default.
• W2044098466 cites W1999724806 @default.
• W2044098466 cites W2000980755 @default.
• W2044098466 cites W2004360551 @default.
• W2044098466 cites W2006102455 @default.
• W2044098466 cites W2006903449 @default.
• W2044098466 cites W2007054796 @default.
• W2044098466 cites W2007301879 @default.
• W2044098466 cites W2008856178 @default.
• W2044098466 cites W2010849549 @default.
• W2044098466 cites W2014880911 @default.
• W2044098466 cites W2015039690 @default.
• W2044098466 cites W2015838019 @default.
• W2044098466 cites W2016421452 @default.
• W2044098466 cites W2021534482 @default.
• W2044098466 cites W2022464713 @default.
• W2044098466 cites W2023387870 @default.
• W2044098466 cites W2026552146 @default.
• W2044098466 cites W2026911129 @default.
• W2044098466 cites W2030186450 @default.
• W2044098466 cites W2030419415 @default.
• W2044098466 cites W2031570130 @default.
• W2044098466 cites W2032897685 @default.
• W2044098466 cites W2035407823 @default.
• W2044098466 cites W2036013980 @default.
• W2044098466 cites W2039505705 @default.
• W2044098466 cites W2039532499 @default.
• W2044098466 cites W2040407044 @default.
• W2044098466 cites W2052264682 @default.
• W2044098466 cites W2052380879 @default.
• W2044098466 cites W2054403251 @default.
• W2044098466 cites W2055689823 @default.
• W2044098466 cites W2056511887 @default.
• W2044098466 cites W2059791596 @default.
• W2044098466 cites W2060099174 @default.
• W2044098466 cites W2060515155 @default.
• W2044098466 cites W2063109965 @default.
• W2044098466 cites W2064811345 @default.
• W2044098466 cites W2067484870 @default.
• W2044098466 cites W2072207242 @default.
• W2044098466 cites W2073872759 @default.
• W2044098466 cites W2075369230 @default.
• W2044098466 cites W2075705506 @default.
• W2044098466 cites W2077141405 @default.
• W2044098466 cites W2082006283 @default.
• W2044098466 cites W2084949662 @default.
• W2044098466 cites W2088968192 @default.
• W2044098466 cites W2093674123 @default.
• W2044098466 cites W2094280270 @default.
• W2044098466 cites W2095398138 @default.
• W2044098466 cites W2095805596 @default.
• W2044098466 cites W2099454812 @default.
• W2044098466 cites W2106315897 @default.
• W2044098466 cites W2106320506 @default.
• W2044098466 cites W2112194058 @default.
• W2044098466 cites W2125323855 @default.
• W2044098466 cites W2139853103 @default.
• W2044098466 cites W2140038584 @default.
• W2044098466 cites W2144119289 @default.
• W2044098466 cites W2151366285 @default.
• W2044098466 cites W2152549153 @default.
• W2044098466 cites W2153825083 @default.
• W2044098466 cites W2172063293 @default.
• W2044098466 cites W4230223507 @default.
• W2044098466 doi "https://doi.org/10.1016/s0006-3495(02)75302-2" @default.

• next