SynopsisSerum albumin undergoes a conformational change a t pH 4, known as the N-F transition. In the customary LinderstrZm-Lang treatment of hydrogen ion titration, the carboxyl groups in serum albumin either have an abnormally low pK, or are buried in charged form, and the LinderstrZm-Lang charging parameter w decreases dramatically at the N-F isomerization. In the present paper partition functions are derived and distribution functions are calculated for a model permitting salt bonding between the positively and negatively charged sites on a macromolecule. The N-form has an abnormally high salt bonding constant whereas that of the F-form corresponds to that of small ions. The result obtained is consistent with a "normal" intrinsic pK of the carboxyl groups of serum albumin without burying of any charges and with an unchanged W.Further, it is shown that the "abnormal salt bonding" of serum album'n can explain its unusual ability to bind anions. Theoretical binding curves are calculated and compared with literature data of the C1-binding of serum albumin. The relation of the present model to other models of hydrogen ion and anion binding to proteins is discussed. Some additional consequences of the present model are pointed out; a transition in the alkaline range, analogous to the acid transition, seems probable. Literature data support the existence of such a transition but do not allow detailed calculations a t present.A general, thermodynamic treatment of the interactions between small ligands and macromolecules is outlined. Important points are the choice of the statistical-mechanical ensemble and considerations of the fluctuations about the mean binding, if (i)there are not only a ligand-locus interaction but also interligand interactions (in particular intdigand attraction), or (ii) there is a conformational change in themacromolecule depending on the ligand binding. In these cases, the binding isotherms obtained from thermodynamically closed systems (canonical ensemble)) may erroneously indicate a distribution about a single probability maximum, i.e., the statistical mean binding N, and fluctuations about this value. The description of a phase change in a bound phase or a change in the "internal" self-interactions of a macromolecule requires a binding equation permitting distributions about two maxima, i.e., (i) N1* < iV ("thin" phase) and Nz* > iV (L'condensed" phase) or (ii) two macromolecular conformations P', and P", having occupancy numbers iV, and ITz, respectively. The N-F transition is an example illustrating the relation between the complete distribution functions and the two-state approximation. 2197
Previous studies on small molecule—protein interactions by the present author and studies on the denaturation of serum albumin by Gorbacheva et al. and by Janatová indicate that the tertiary structure of the native serum albumin molecule does not represent the thermodynamically most probable conformation. It is suggested that the amino and carboxyl groups of the albumin molecule are locked into positions which are metastable with respect to solvent, probably by means of the S—S bonds. The resulting intramolecular interactions (“salt bonding”) in serum albumin then affect intermolecular interactions as manifested by its “abnormal” binding properties. These interactions should also be considered when discussing “abnormal” titration and denaturation properties as an alternative to masking of groups and/or heterogeneity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.