scholarly journals A Distal Point Mutation in the Streptavidin−Biotin Complex Preserves Structure but Diminishes Binding Affinity: Experimental Evidence of Electronic Polarization Effects?

Biochemistry ◽  
2010 ◽  
Vol 49 (22) ◽  
pp. 4568-4570 ◽  
Author(s):  
Loren Baugh ◽  
Isolde Le Trong ◽  
David S. Cerutti ◽  
Susanne Gülich ◽  
Patrick S. Stayton ◽  
...  
Keyword(s):  
Experimental Evidence ◽  
Point Mutation ◽  
Binding Affinity ◽  
Electronic Polarization ◽  
Polarization Effects ◽  
Distal Point

scholarly journals Hypertrophic cardiomyopathy MYH7 mutation R723G alters mRNA secondary structure

2020 ◽  
Vol 52 (1) ◽  
pp. 15-19
Author(s):  
J. Rose ◽  
T. Kraft ◽  
B. Brenner ◽  
J. Montag
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Secondary Structure ◽  
Experimental Evidence ◽  
Point Mutation ◽  
Shape Analysis ◽  
Allelic Imbalance ◽  
Mrna Secondary Structure ◽  
Wild Type ◽  
Mrna Structure

Point mutation R723G in the MYH7 gene causes hypertrophic cardiomyopathy (HCM). Heterozygous patients with this mutation exhibit a comparable allelic imbalance of the MYH7 gene. On average 67% of the total MYH7 mRNA are derived from the MYH7R723G-allele and 33% from the MYH7WT allele. Mechanisms underlying mRNA allelic imbalance are largely unknown. We suggest that a different mRNA lifetime of the alleles may cause the allelic drift in R723G patients. A potent regulator of mRNA lifetime is its secondary structure. To test for alterations in the MYH7R723G mRNA structure we used selective 2′-hydroxyl acylation analyzed by primer extension (SHAPE) analysis. We show significantly different SHAPE reactivity of wild-type and MYH7R723G RNA, which is in accordance with bioinformatically predicted structures. Thus, we provide the first experimental evidence for mRNA secondary structure alterations by the HCM point mutation. We assume that this may result in a prolonged lifetime of MYH7R723G mRNA in vivo and subsequently in the determined allelic imbalance.

Mutation of G51 in SepF impairs FtsZ assembly promoting ability of SepF and retards the division of Mycobacterium smegmatis cells

2018 ◽  
Vol 475 (15) ◽  
pp. 2473-2489
Author(s):  
Dipanwita Bhattacharya ◽  
Kanchan Sinha ◽  
Dulal Panda
Keyword(s):  
Point Mutation ◽  
Binding Affinity ◽  
Mycobacterium Smegmatis ◽  
Average Length ◽  
Gtpase Activity ◽  
Associated Proteins ◽  
Dominant Point ◽  
Ftsz Assembly

The role of FtsZ-associated proteins in the regulation of the assembly dynamics of Mycobacterium smegmatis FtsZ is not clear. In this work, we examined the effect of M. smegmatis SepF on the assembly and stability of M. smegmatis FtsZ polymers. We discovered a single dominant point mutation in SepF (G51D or G51R) that renders the protein inactive. SepF promoted the polymerization of FtsZ, induced the bundling of FtsZ filaments, stabilized FtsZ filaments and reduced the GTPase activity of FtsZ. Surprisingly, both G51D-SepF and G51R-SepF neither stabilized FtsZ filaments nor showed a discernable effect on the GTPase activity of FtsZ. The binding affinity of SepF to FtsZ was found to be stronger than the binding affinity of G51R/D-SepF to FtsZ. Interestingly, the binding affinity of SepF to G51R-SepF was determined to be 45 times stronger than FtsZ. In addition, the interaction of SepF with G51R-SepF was found to be 2.6 times stronger than SepF–SepF interaction. Furthermore, G51R-SepF impaired the ability of SepF to promote the assembly of FtsZ. In addition, the overexpression of G51R-SepF in M. smegmatis mc2 155 cells retarded the proliferation of these cells and increased the average length of the cells. The results indicated that SepF positively regulates the assembly of M. smegmatis FtsZ and the G51 residue has an important role in the functioning of SepF.

scholarly journals Preorganization in biological systems: Are conformational constraints worth the energy?

2007 ◽  
Vol 79 (2) ◽  
pp. 193-200 ◽  
Author(s):  
Stephen F. Martin
Keyword(s):  
Experimental Evidence ◽  
Binding Affinity ◽  
Three Dimensional ◽  
Common Belief ◽  
Flexible Control ◽  
Protein Ligand Interactions ◽  
Conformational Constraints ◽  
Ligand Interactions ◽  
Dimensional Shape ◽  
Three Dimensional Shape

It is generally assumed that preorganizing a flexible ligand in the three-dimensional shape it adopts when bound to a macromolecular receptor will provide a derivative having an increased binding affinity, primarily because the rigidified molecule is expected to benefit from a lesser entropic penalty during complexation. We now provide the first experimental evidence that demonstrates this common belief is not universally true. Indeed, we find that ligand preorganization may be accompanied by an unfavorable entropy of binding, even when the constrained ligand exhibits a higher binding affinity than its flexible control. Thus, the effects that ligand preorganization have upon energetics and structure in protein-ligand interactions must be reevaluated.

Solvent Electronic Polarization Effects on Na+–Na+ and Cl––Cl– Pair Associations in Aqueous Solution

2013 ◽  
Vol 117 (31) ◽  
pp. 9273-9279 ◽  
Author(s):  
Cheol Ho Choi ◽  
Suyong Re ◽  
Mohammad H. O. Rashid ◽  
Hui Li ◽  
Michael Feig ◽  
...  
Keyword(s):  
Aqueous Solution ◽  
Electronic Polarization ◽  
Polarization Effects

Experimental evidence of polarization effects on exchangeable cations trapped in zeolites

2000 ◽  
Vol 113 (11) ◽  
pp. 4498-4500 ◽  
Author(s):  
J. C. Giuntini ◽  
G. Maurin ◽  
S. Devautour ◽  
F. Henn ◽  
J. V. Zanchetta
Keyword(s):  
Experimental Evidence ◽  
Exchangeable Cations ◽  
Polarization Effects

Relationship between a point mutation S97C in CK1δ protein and its affect on ATP-binding affinity

2013 ◽  
Vol 32 (3) ◽  
pp. 394-405 ◽  
Author(s):  
Ambuj Kumar ◽  
Vidya Rajendran ◽  
Rao Sethumadhavan ◽  
Rituraj Purohit
Keyword(s):  
Point Mutation ◽  
Binding Affinity ◽  
Atp Binding
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