Disease mutation study identifies essential residues for phosphatidylserine flippase ATP11A

AbstractPS flippase (P4-ATPase) transports PS from the outer to the inner leaflet of the lipid bilayer in the membrane to maintain PS asymmetry, which is important for biological activity of the cell. ATP11A is expressed in multiple tissues and plays a role in myotube formation. However, detailed cellular function of ATP11A remains elusive. Mutation analysis revealed that I91, L308 and E897 residues in ATP8A2 are important for flippase activity. In order to investigate the roles of these corresponding amino acid residues in ATP11A, we assessed the expression and flippase activity of the respective ATP11A mutant proteins. ATP11A mainly localizes to the Golgi when co-expressed with TMEM30A, the β-subunit of the complex. Y300F and D913K mutations affect correct Golgi localization and PS stimulated flippase activity. In addition, Y300F mutation causes reduced ATP11A expression. Our data provides insight into essential residues for expression and flippase activity of ATP11A.

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Disease Mutation Study Identifies Critical Residues for Phosphatidylserine Flippase ATP11A

BioMed Research International ◽

10.1155/2020/7342817 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Kuanxiang Sun ◽

Wanli Tian ◽

Xiao Li ◽

Wenjing Liu ◽

Yeming Yang ◽

...

Keyword(s):

Plasma Membrane ◽

Amino Acid ◽

Lipid Bilayer ◽

Cellular Localization ◽

Biological Activities ◽

Amino Acid Residues ◽

Mutant Proteins ◽

Myotube Formation ◽

Critical Residues ◽

Insight Into

Phosphatidylserine flippase (P4-ATPase) transports PS from the outer to the inner leaflet of the lipid bilayer in the membrane to maintain PS asymmetry, which is important for biological activities of the cell. ATP11A is expressed in multiple tissues and plays a role in myotube formation. However, the detailed cellular function of ATP11A remains elusive. Mutation analysis revealed that I91, L308, and E897 residues in ATP8A2 are important for flippase activity. In order to investigate the roles of these corresponding amino acid residues in ATP11A protein, we assessed the expression and cellular localization of the respective ATP11A mutant proteins. ATP11A mainly localizes to the Golgi and plasma membrane when coexpressed with the β-subunit of the complex TMEM30A. Y300F mutation causes reduced ATP11A expression, and Y300F and D913K mutations affect correct localization of the Golgi and plasma membrane. In addition, Y300F and D913K mutations also affect PS flippase activity. Our data provides insight into important residues of ATP11A.

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Biological Function and Chemistry of Endothelin. A Review

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19991211 ◽

1999 ◽

Vol 64 (8) ◽

pp. 1211-1252 ◽

Cited By ~ 4

Author(s):

Jan Hlaváček ◽

Renáta Marcová

Keyword(s):

Biological Activity ◽

Amino Acid ◽

Biological Function ◽

Biological Properties ◽

Structural Basis ◽

Amino Acid Residues ◽

Snake Venoms ◽

Vasoactive Peptides ◽

Physico Chemical ◽

Endothelin A

The first part of this review deals with the biosynthesis and a biological function of strongly vasoactive peptides named endothelins (ETs) including vasoactive intestinal contractor. Where it was useful, snake venoms sarafotoxins which are structural endothelin derivatives, were also mentioned. In the second part, an attention is paid to structural basis of the ETs biological activity, with respect to alterations of amino acid residues in the parent peptides modifying the conformation and consequently the physico-chemical and biological properties in corresponding ETs analogs. Special attention is focussed on the area of ETs receptors and their interaction with peptide and non peptide agonists and antagonists, important in designing selective inhibitors of ETs receptors potentially applicable as drugs in a medicine. A review with 182 references.

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Insight into the mechanism of thermostabilization of GH10 xylanase from Bacillus sp. strain TAR-1 by the mutation of S92 to E

Bioscience Biotechnology and Biochemistry ◽

10.1093/bbb/zbaa003 ◽

2021 ◽

Vol 85 (2) ◽

pp. 386-390

Author(s):

Manami Suzuki ◽

Teisuke Takita ◽

Kohei Kuwata ◽

Kota Nakatani ◽

Tongyang Li ◽

...

Keyword(s):

Amino Acid ◽

Thermodynamic Analysis ◽

Thermal Inactivation ◽

Entropy Change ◽

Crystallographic Analysis ◽

Bacillus Sp ◽

Amino Acid Residues ◽

Gh10 Xylanase ◽

Insight Into

ABSTRACT The mechanism of thermostabilization of GH10 xylanase, XynR, from Bacillus sp. strain TAR-1 by the mutation of S92 to E was investigated. Thermodynamic analysis revealed that thermostabilization was driven by the decrease in entropy change of activation for thermal inactivation. Crystallographic analysis suggested that this mutation suppressed the fluctuation of the amino acid residues at position 92-95.

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Metal complexes of polymers with amino acid residues. formation, stability and controlled biological activity

Journal of Controlled Release ◽

10.1016/0168-3659(90)90061-w ◽

1990 ◽

Vol 14 (1) ◽

pp. 61-70 ◽

Cited By ~ 11

Author(s):

V.A. Lee ◽

R.I. Musin ◽

R.I. Tashmukhamedov ◽

M.I. Shtilman ◽

S.Sh. Rashidova

Keyword(s):

Biological Activity ◽

Amino Acid ◽

Metal Complexes ◽

Amino Acid Residues

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Location of antigenic sites recognized by monoclonal antibodies in the influenza A virus nucleoprotein molecule

Journal of General Virology ◽

10.1099/vir.0.010660-0 ◽

2009 ◽

Vol 90 (7) ◽

pp. 1730-1733 ◽

Cited By ~ 8

Author(s):

Natalia L. Varich ◽

Konstantin S. Kochergin-Nikitsky ◽

Evgeny V. Usachev ◽

Olga V. Usacheva ◽

Alexei G. Prilipov ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Amino Acid ◽

Influenza A Virus ◽

Influenza A ◽

Antigenic Variation ◽

Strain Differences ◽

Antigenic Structure ◽

Amino Acid Residues ◽

Mutant Proteins ◽

Antigenic Sites

The locations of amino acid positions relevant to antigenic variation in the nucleoprotein (NP) of influenza virus are not conclusively known. We analysed the antigenic structure of influenza A virus NP by introducing site-specific mutations at amino acid positions presumed to be relevant for the differentiation of strain differences by anti-NP monoclonal antibodies. Mutant proteins were expressed in a prokaryotic system and analysed by performing ELISA with monoclonal antibodies. Four amino acid residues were found to determine four different antibody-binding sites. When mapped in a 3D X-ray model of NP, the four antigenically relevant amino acid positions were found to be located in separate physical sites of the NP molecule.

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The effect of modifications of the A5 and A19 amino acid residues on the biological activity of insulin. [Leu5-A] and [Phe19-A] sheep insulins

Journal of Protein Chemistry ◽

10.1007/bf01025378 ◽

1983 ◽

Vol 2 (2) ◽

pp. 147-170 ◽

Cited By ~ 13

Author(s):

Nicolaos Ferderigos ◽

G. Thompson Burke ◽

Kouki Kitagawa ◽

Panayotis G. Katsoyannis

Keyword(s):

Biological Activity ◽

Amino Acid ◽

Amino Acid Residues

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Structure-activity studies of dermorphin. The role of side chains of amino acid residues on the biological activity of dermorphin

Peptides ◽

10.1016/0196-9781(84)90007-x ◽

1984 ◽

Vol 5 (4) ◽

pp. 687-689 ◽

Cited By ~ 15

Author(s):

Krzysztof Darłak ◽

Zbigniew Grzonka ◽

Pawel Krzaścik ◽

Piotr Janicki ◽

S.Witold Gumułka

Keyword(s):

Biological Activity ◽

Amino Acid ◽

Side Chains ◽

Amino Acid Residues ◽

Structure Activity

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Structure–function studies of human deoxyhypusine synthase: identification of amino acid residues critical for the binding of spermidine and NAD

Biochemical Journal ◽

10.1042/bj3550841 ◽

2001 ◽

Vol 355 (3) ◽

pp. 841-849 ◽

Cited By ~ 21

Author(s):

Chang Hoon LEE ◽

Patrick Y. UM ◽

Myung Hee PARK

Keyword(s):

Crystal Structure ◽

Enzyme Activity ◽

Amino Acid ◽

Binding Sites ◽

Binding Pocket ◽

Complete Loss ◽

Amino Acid Residues ◽

Deoxyhypusine Synthase ◽

Positive Identification ◽

Insight Into

Deoxyhypusine synthase catalyses the first step in the biosynthesis of hypusine [Nε-(4-amino-2-hydroxybutyl)lysine]. The crystal structure of human deoxyhypusine synthase in complex with NAD revealed four NAD-binding sites per enzyme tetramer, and led to a prediction of the spermidine-binding pocket. We have replaced each of the seven amino acid residues at the predicted spermidine-binding site, and eleven residues that contact NAD, on an individual basis with alanine. Of the amino acid residues at the spermidine site, substitution of Asp-243, Trp-327, His-288, Asp-316 or Glu-323 with alanine caused an almost complete loss of spermidine binding and enzyme activity; only the mutation Tyr-305 → Ala showed partial binding and activity. His-288 → Ala was also deficient in terms of binding NAD. NAD binding was significantly reduced in all of the NAD-site mutant enzymes, except for Glu-137 → Ala, which showed a normal binding of NAD, but was totally lacking in spermidine binding. Of the NAD-site mutant enzymes, Asp-342 → Ala, Asp-313 → Ala and Asp-238 → Ala displayed the lowest binding of NAD. These enzymes and His-288Ala also showed a reduced binding of spermidine, presumably because spermidine binding is dependent on NAD. These findings permit the positive identification of amino acid residues critical for binding of spermidine and NAD, and provide a new insight into the complex molecular interactions involved in the deoxyhypusine synthase reaction.

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