Hydrophobic Amino Acid Residues of Human Anticoagulation Protein C That Contribute to Its Functional Binding to Phospholipid Vesicles

Biochemistry ◽  
1995 ◽  
Vol 34 (33) ◽  
pp. 10376-10382 ◽  
Author(s):  
William T. Christiansen ◽  
Louise R. Jalbert ◽  
Rolanda M. Robertson ◽  
Ashish Jhingan ◽  
Mary Prorok ◽  
...  
Keyword(s):  
Amino Acid ◽  
Protein C ◽  
Phospholipid Vesicles ◽  
Amino Acid Residues ◽  
Hydrophobic Amino Acid

scholarly journals Mitigating the Adverse Effects of Polychlorinated Biphenyl Derivatives on Estrogenic Activity via Molecular Modification Techniques

2021 ◽  
Vol 18 (9) ◽  
pp. 4999
Author(s):  
Wei He ◽  
Wenhui Zhang ◽  
Zhenhua Chu ◽  
Yu Li
Keyword(s):  
Amino Acid ◽  
Binding Site ◽  
Hydrophobic Interaction ◽  
Oestrogen Receptor ◽  
Polychlorinated Biphenyl ◽  
Hydrophobic Interactions ◽  
Estrogenic Activity ◽  
Average Distance ◽  
Amino Acid Residues ◽  
Hydrophobic Amino Acid

The aim of this paper is to explore the mechanism of the change in oestrogenic activity of PCBs molecules before and after modification by designing new PCBs derivatives in combination with molecular docking techniques through the constructed model of oestrogenic activity of PCBs molecules. We found that the weakened hydrophobic interaction between the hydrophobic amino acid residues and hydrophobic substituents at the binding site of PCB derivatives and human oestrogen receptor alpha (hERα) was the main reason for the weakened binding force and reduced anti-oestrogenic activity. It was consistent with the information that the hydrophobic field displayed by the 3D contour maps in the constructed oestrogen activity CoMSIA model was one of the main influencing force fields. The hydrophobic interaction between PCB derivatives and oestrogen-active receptors was negatively correlated with the average distance between hydrophobic substituents and hydrophobic amino acid residues at the hERα-binding site, and positively correlated with the number of hydrophobic amino acid residues. In other words, the smaller the average distance between the hydrophobic amino acid residues at the binding sites between the two and the more the number of them, and the stronger the oestrogen activity expression degree of PCBS derivative molecules. Therefore, hydrophobic interactions between PCB derivatives and the oestrogen receptor can be reduced by altering the microenvironmental conditions in humans. This reduces the ability of PCB derivatives to bind to the oestrogen receptor and can effectively modulate the risk of residual PCB derivatives to produce oestrogenic activity in humans.

Enhanced stability of Cu2+–ATCUN complexes under physiologically relevant conditions by insertion of structurally bulky and hydrophobic amino acid residues into the ATCUN motif

2016 ◽  
Vol 45 (23) ◽  
pp. 9436-9445 ◽  
Author(s):  
Takaaki Miyamoto ◽  
Yuta Fukino ◽  
Shinichiro Kamino ◽  
Masashi Ueda ◽  
Shuichi Enomoto
Keyword(s):  
Amino Acid ◽  
Amino Acid Residues ◽  
Hydrophobic Amino Acid ◽  
Hydrophobic Residues ◽  
The Stability ◽  
Enhanced Stability

The stability of Cu2+–ATCUN complexes under physiologically relevant conditions is enhanced by inserting bulky and hydrophobic residues at positions 1 and 2 of the ATCUN peptide.

Molecular Basis for A Thrombophilic Patient's Combined Deficiencies in Proteins C and S.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4198-4198
Author(s):  
Tyler W Smith ◽  
Isis S. R Carter ◽  
Cedric John Carter ◽  
Ross T.A MacGillivray
Keyword(s):  
Amino Acid ◽  
Dna Sequences ◽  
Promoter Region ◽  
Protein C ◽  
Conflicts Of Interest ◽  
Genetic Defect ◽  
Protein S ◽  
Catalytic Triad ◽  
Chromosome 2 ◽  
Amino Acid Residues

Abstract Abstract 4198 Background/objectives Proteins C and S (PC and PS) are vitamin K-dependent plasma proteins with anticoagulant properties. Protein S functions as a non-enzymatic cofactor for activated protein C (APC). APC proteolytically degrades coagulation factors Va and VIIIa, thereby diminishing the activities of the prothrombinase and tenase complexes, respectively. The human PC gene (PROC) is located on the long arm of chromosome 2 (2q13-q14) and contains 9 exons which code for 461 amino acid residues. The human PS (PROS1) gene resides on chromosome 3 (3p11.1-q11.2) and contains 15 exons coding for 636 amino acid residues. Hereditary PS and PC deficiencies are both autosomal dominant disorders in which patients have diminished functional levels of the respective protein (usually ∼50% relative to normal controls). Clinically, this results in increased propensity toward thromboembolic disease, also known as thrombophilia. In this study, we describe a unique thrombophilic patient who has combined deficiencies in both proteins C and S. The objective of the study was to elucidate the precise genetic defect(s) causing these deficiencies. Methods Following purification of the patient's DNA from peripheral blood leukocytes, PCR amplifications were performed using oligonucleotide primers flanking all exons of the PROS1 and PROC genes. In addition, the 400bp region upstream of the first exon of PROS1 (corresponding to the promoter region) was also amplified by PCR. The PCR products were purified and their DNA sequences determined in both forward and reverse directions using the dye-terminator method. The resultant nucleotide sequences were compared with the PROS1 and PROC reference sequences [web address]. Results The patient was found to be heterozygous for a novel missense PROC gene mutation in exon 8, which codes in part for the proteolytic domain of protein C. The resulting ValàGly substitution of residue 221 is in close proximity to the catalytic triad, which could abrogate its enzymatic activity. Although no mutations were present in any of the patient's PROS1 exons, there was a novel heterozygous CàG nucleotide substitution in the PROS1 promoter region. This substitution is present within an Sp1 transcription factor binding site that is highly conserved among mammals. Therefore, this mutation could significantly diminish expression of the otherwise normal PROS1 gene, leading to the observed decreased protein S level. Both mutations are unreported in the literature and are not listed in the PROC and PROS1 mutation databases. Conclusions We have successfully identified two novel genetic defects leading to deficiencies of the anticoagulant proteins C and S in a patient with thrombophilia. Further studies are underway to confirm the suggested biochemical effects of the mutation on protein C and protein S gene expression. Disclosures: No relevant conflicts of interest to declare.

Freezing-induced exposure of hydrophobic amino acid residues from actomyosin.

1986 ◽  
Vol 52 (5) ◽  
pp. 859-862 ◽  
Author(s):  
Eiji Niwa ◽  
Shin-ichiro Kohda ◽  
Teruo Nakayama
Keyword(s):  
Amino Acid ◽  
Amino Acid Residues ◽  
Hydrophobic Amino Acid
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