Energetics of a hydrogen bond (charged and neutral) and of a cation-pi interaction in apoflavodoxin.


Anabaena apoflavodoxin contains a single histidine residue (H34) that interacts with two aromatic residues (F7 and Y47). The histidine and phenylalanine rings are almost coplanar and they can establish a cation-pi interaction when the histidine is protonated. The histidine and tyrosine side-chains are engaged in a hydrogen bond, which is their only contact. We analyse the energetics of these interactions using p Ka-shift analysis, double-mutant cycle analysis at two pH values, and X-ray crystallography. The H/F interaction is very weak when the histidine is neutral, but it is strengthened by 0.5 kcal mol-1on histidine protonation. Supporting this fact, the histidine p Kain a F7L mutant is 0.4 pH units lower than in wild-type. The strength of the H/Y hydrogen bond is 0.7 kcal mol-1when the histidine is charged, and it becomes stronger (1.3 kcal mol-1) when the histidine is neutral. This is consistent with our observation that the (H34)Nepsilon2-OH(Y47) distance is slightly shorter in the apoflavodoxin structure at pH 9.0 than in the previously reported structure at pH 6.0. It is also consistent with a histidine p Kavalue 0.6 pH units higher in a Y47F mutant than in the wild-type protein. We suggest that the higher stability of the neutral hydrogen bond could be due to a higher desolvation penalty of the charged hydrogen bond that would offset its more favourable enthalpy of formation. The relationship between hydrogen bond strength and the contribution of hydrogen bonds to protein stability is discussed. Study holds ProTherm entries: 6203, 6204, 6205, 6206, 6207, 6208, 6209, 6210, 6211, 6212, 6213, 6214 Extra Details: hydrogen bond; cation-pi interaction; histidine p Ka;,flavodoxin; protein stability

Submission Details

ID: VTzMC27c

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:31 p.m.

Version: 1

Publication Details
Fernández-Recio J;Romero A;Sancho J,J. Mol. Biol. (1999) Energetics of a hydrogen bond (charged and neutral) and of a cation-pi interaction in apoflavodoxin. PMID:10388575
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 Flavodoxin P0A3D9 FLAV_NOSS1
100.0 Flavodoxin P0A3E0 FLAV_NOSSO