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Article: Vibrio

Herrera, Alfa / Packer, Megan M / Rosas-Lemus, Monica / Minasov, George / Brummel, John H / Satchell, Karla J F

bioRxiv : the preprint server for biology

2023

Abstract: ... Vibrio ... ...

Abstract	Vibrio vulnificus
Language	English
Publishing date	2023-05-12
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.04.19.537381
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Article ; Online: Serodominant SARS-CoV-2 Nucleocapsid Peptides Map to Unstructured Protein Regions.

Vandervaart, Jacob P / Inniss, Nicole L / Ling-Hu, Ted / Minasov, George / Wiersum, Grant / Rosas-Lemus, Monica / Shuvalova, Ludmilla / Achenbach, Chad J / Hultquist, Judd F / Satchell, Karla J F / Bachta, Kelly E R

Microbiology spectrum

2023 Volume 11, Issue 3, Page(s) e0032423

Abstract: The SARS-CoV-2 nucleocapsid (N) protein is highly immunogenic, and anti-N antibodies are commonly used as markers for prior infection. While several studies have examined or predicted the antigenic regions of N, these have lacked consensus and structural ...

Abstract	The SARS-CoV-2 nucleocapsid (N) protein is highly immunogenic, and anti-N antibodies are commonly used as markers for prior infection. While several studies have examined or predicted the antigenic regions of N, these have lacked consensus and structural context. Using COVID-19 patient sera to probe an overlapping peptide array, we identified six public and four private epitope regions across N, some of which are unique to this study. We further report the first deposited X-ray structure of the stable dimerization domain at 2.05 Å as similar to all other reported structures. Structural mapping revealed that most epitopes are derived from surface-exposed loops on the stable domains or from the unstructured linker regions. An antibody response to an epitope in the stable RNA binding domain was found more frequently in sera from patients requiring intensive care. Since emerging amino acid variations in N map to immunogenic peptides, N protein variation could impact detection of seroconversion for variants of concern.
MeSH term(s)	Humans ; SARS-CoV-2 ; Intrinsically Disordered Proteins ; COVID-19 ; Antibodies, Viral ; Epitopes ; Nucleocapsid ; Peptides
Chemical Substances	Intrinsically Disordered Proteins ; Antibodies, Viral ; Epitopes ; Peptides
Language	English
Publishing date	2023-05-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.00324-23
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Article ; Online: A high-throughput structural system biology approach to increase structure representation of proteins from

Rosas-Lemus, Monica / Dey, Supratim / Minasov, George / Tan, Kemin / Anderson, Spencer M / Brunzelle, Joseph / Nocadello, Salvatore / Shabalin, Ivan / Filippova, Ekaterina / Halavaty, Andrei / Kim, Youngchang / Maltseva, Natalia / Osipiuk, Jerzy / Minor, Wladek / Joachimiak, Andrzej / Savchenko, Alexei / Anderson, Wayne F / Satchell, Karla J F

Microbiology resource announcements

2023 Volume 12, Issue 10, Page(s) e0050723

Abstract: Clostridioides ... ...

Abstract	Clostridioides difficile
Language	English
Publishing date	2023-09-25
Publishing country	United States
Document type	Journal Article
ISSN	2576-098X
ISSN (online)	2576-098X
DOI	10.1128/MRA.00507-23
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Article ; Online: Functional and Structural Characterization of OXA-935, a Novel OXA-10-Family β-Lactamase from Pseudomonas aeruginosa.

Pincus, Nathan B / Rosas-Lemus, Monica / Gatesy, Samuel W M / Bertucci, Hanna K / Brunzelle, Joseph S / Minasov, George / Shuvalova, Ludmilla A / Lebrun-Corbin, Marine / Satchell, Karla J F / Ozer, Egon A / Hauser, Alan R / Bachta, Kelly E R

Antimicrobial agents and chemotherapy

2022 Volume 66, Issue 10, Page(s) e0098522

Abstract: Resistance to antipseudomonal penicillins and cephalosporins is often driven by the overproduction of the intrinsic β-lactamase AmpC. However, OXA-10-family β-lactamases are a rich source of resistance in Pseudomonas aeruginosa. OXA β-lactamases have a ... ...

Abstract	Resistance to antipseudomonal penicillins and cephalosporins is often driven by the overproduction of the intrinsic β-lactamase AmpC. However, OXA-10-family β-lactamases are a rich source of resistance in Pseudomonas aeruginosa. OXA β-lactamases have a propensity for mutation that leads to extended spectrum cephalosporinase and carbapenemase activity. In this study, we identified isolates from a subclade of the multidrug-resistant (MDR) high risk P. aeruginosa clonal complex CC446 with a resistance to ceftazidime. A genomic analysis revealed that these isolates harbored a plasmid containing a novel allele of
MeSH term(s)	Humans ; Ceftazidime/pharmacology ; Pseudomonas aeruginosa ; beta-Lactamase Inhibitors/pharmacology ; Cephalosporinase/genetics ; Aspartic Acid ; Microbial Sensitivity Tests ; Anti-Bacterial Agents/pharmacology ; Tazobactam/pharmacology ; beta-Lactamases/genetics ; beta-Lactamases/metabolism ; Cephalosporins/pharmacology ; Azabicyclo Compounds/pharmacology ; Serine ; Phenylalanine ; Glycine ; Pseudomonas Infections/drug therapy
Chemical Substances	Ceftazidime (9M416Z9QNR) ; beta-lactamase PSE-2 (EC 3.5.2.-) ; beta-Lactamase Inhibitors ; Cephalosporinase (EC 3.5.2.-) ; Aspartic Acid (30KYC7MIAI) ; Anti-Bacterial Agents ; Tazobactam (SE10G96M8W) ; beta-Lactamases (EC 3.5.2.6) ; Cephalosporins ; Azabicyclo Compounds ; Serine (452VLY9402) ; Phenylalanine (47E5O17Y3R) ; Glycine (TE7660XO1C)
Language	English
Publishing date	2022-09-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	217602-6
ISSN	1098-6596 ; 0066-4804
ISSN (online)	1098-6596
ISSN	0066-4804
DOI	10.1128/aac.00985-22
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Article ; Online: Age-Dependent Decline in Synaptic Mitochondrial Function Is Exacerbated in Vulnerable Brain Regions of Female 3xTg-AD Mice.

Espino de la Fuente-Muñoz, César / Rosas-Lemus, Mónica / Moreno-Castilla, Perla / Bermúdez-Rattoni, Federico / Uribe-Carvajal, Salvador / Arias, Clorinda

International journal of molecular sciences

2020 Volume 21, Issue 22

Abstract: Synaptic aging has been associated with neuronal circuit dysfunction and cognitive decline. Reduced mitochondrial function may be an early event that compromises synaptic integrity and neurotransmission in vulnerable brain regions during physiological ... ...

Abstract	Synaptic aging has been associated with neuronal circuit dysfunction and cognitive decline. Reduced mitochondrial function may be an early event that compromises synaptic integrity and neurotransmission in vulnerable brain regions during physiological and pathological aging. Thus, we aimed to measure mitochondrial function in synapses from three brain regions at two different ages in the 3xTg-AD mouse model and in wild mice. We found that aging is the main factor associated with the decline in synaptic mitochondrial function, particularly in synapses isolated from the cerebellum. Accumulation of toxic compounds, such as tau and Aβ, that occurred in the 3xTg-AD mouse model seemed to participate in the worsening of this decline in the hippocampus. The changes in synaptic bioenergetics were also associated with increased activation of the mitochondrial fission protein Drp1. These results suggest the presence of altered mechanisms of synaptic mitochondrial dynamics and their quality control during aging and in the 3xTg-AD mouse model; they also point to bioenergetic restoration as a useful therapeutic strategy to preserve synaptic function during aging and at the early stages of Alzheimer's disease (AD).
MeSH term(s)	Aging/genetics ; Aging/metabolism ; Amyloid beta-Peptides/genetics ; Amyloid beta-Peptides/metabolism ; Animals ; Cerebellum/metabolism ; Cerebellum/physiopathology ; Cerebral Cortex/metabolism ; Cerebral Cortex/physiopathology ; Cognitive Dysfunction/genetics ; Cognitive Dysfunction/metabolism ; Cognitive Dysfunction/physiopathology ; Disease Models, Animal ; Dynamins/genetics ; Dynamins/metabolism ; Female ; Gene Expression Regulation ; Hippocampus/metabolism ; Hippocampus/physiopathology ; Humans ; Membrane Potential, Mitochondrial/genetics ; Mice ; Mice, Transgenic ; Mitochondria/metabolism ; Mitochondria/pathology ; Mitochondrial Dynamics/genetics ; Neurons/metabolism ; Neurons/pathology ; Organ Specificity ; Synapses/metabolism ; Synapses/pathology ; Synaptosomes/metabolism ; Synaptosomes/pathology ; tau Proteins/genetics ; tau Proteins/metabolism
Chemical Substances	Amyloid beta-Peptides ; Mapt protein, mouse ; tau Proteins ; Dnm1l protein, mouse (EC 3.6.5.5) ; Dynamins (EC 3.6.5.5)
Language	English
Publishing date	2020-11-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21228727
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Article ; Online: High-resolution structures of the SARS-CoV-2 2'-

Rosas-Lemus, Monica / Minasov, George / Shuvalova, Ludmilla / Inniss, Nicole L / Kiryukhina, Olga / Brunzelle, Joseph / Satchell, Karla J F

Science signaling

2020 Volume 13, Issue 651

Abstract: There are currently no antiviral therapies specific for SARS-CoV-2, the virus responsible for the global pandemic disease COVID-19. To facilitate structure-based drug design, we conducted an x-ray crystallographic study of the SARS-CoV-2 nsp16-nsp10 2'- ...

Abstract	There are currently no antiviral therapies specific for SARS-CoV-2, the virus responsible for the global pandemic disease COVID-19. To facilitate structure-based drug design, we conducted an x-ray crystallographic study of the SARS-CoV-2 nsp16-nsp10 2'-
MeSH term(s)	Adenosine/analogs & derivatives ; Adenosine/metabolism ; Adenosine/pharmacology ; Betacoronavirus/drug effects ; Betacoronavirus/enzymology ; Binding Sites ; COVID-19 ; Catalytic Domain ; Coronavirus Infections/drug therapy ; Crystallography, X-Ray ; Dimerization ; Genes, Viral/genetics ; Humans ; Methylation ; Methyltransferases/antagonists & inhibitors ; Methyltransferases/chemistry ; Models, Molecular ; Open Reading Frames/genetics ; Pandemics ; Pneumonia, Viral/drug therapy ; Protein Binding ; Protein Conformation ; RNA Cap Analogs/metabolism ; RNA Processing, Post-Transcriptional ; RNA, Viral/metabolism ; S-Adenosylhomocysteine/metabolism ; S-Adenosylmethionine/metabolism ; SARS-CoV-2 ; Structure-Activity Relationship ; Viral Nonstructural Proteins/antagonists & inhibitors ; Viral Nonstructural Proteins/chemistry ; Viral Nonstructural Proteins/metabolism
Chemical Substances	RNA Cap Analogs ; RNA, Viral ; Viral Nonstructural Proteins ; m7GpppA ; S-Adenosylmethionine (7LP2MPO46S) ; S-Adenosylhomocysteine (979-92-0) ; Methyltransferases (EC 2.1.1.-) ; Adenosine (K72T3FS567) ; sinefungin (W2U467CIIL)
Keywords	covid19
Language	English
Publishing date	2020-09-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2417226-1
ISSN	1937-9145 ; 1945-0877
ISSN (online)	1937-9145
ISSN	1945-0877
DOI	10.1126/scisignal.abe1202
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Article ; Online: Discovery of a Druggable, Cryptic Pocket in SARS-CoV-2 nsp16 Using Allosteric Inhibitors.

Inniss, Nicole L / Kozic, Ján / Li, Fengling / Rosas-Lemus, Monica / Minasov, George / Rybáček, Jiří / Zhu, Yingjie / Pohl, Radek / Shuvalova, Ludmilla / Rulíšek, Lubomír / Brunzelle, Joseph S / Bednárová, Lucie / Štefek, Milan / Kormaník, Ján Michael / Andris, Erik / Šebestík, Jaroslav / Li, Alice Shi Ming / Brown, Peter J / Schmitz, Uli /

Saikatendu, Kumar / Chang, Edcon / Nencka, Radim / Vedadi, Masoud / Satchell, Karla J F

ACS infectious diseases

2023 Volume 9, Issue 10, Page(s) 1918–1931

Abstract: A collaborative, open-science team undertook discovery of novel small molecule inhibitors of the SARS-CoV-2 nsp16-nsp10 2'- ...

Abstract	A collaborative, open-science team undertook discovery of novel small molecule inhibitors of the SARS-CoV-2 nsp16-nsp10 2'-
MeSH term(s)	Mice ; Rats ; Animals ; SARS-CoV-2/metabolism ; S-Adenosylmethionine/chemistry ; S-Adenosylmethionine/metabolism ; COVID-19 ; Methyltransferases
Chemical Substances	S-Adenosylmethionine (7LP2MPO46S) ; Methyltransferases (EC 2.1.1.-)
Language	English
Publishing date	2023-09-20
Publishing country	United States
Document type	Journal Article
ISSN	2373-8227
ISSN (online)	2373-8227
DOI	10.1021/acsinfecdis.3c00203
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Article: A mechanism that transduces lysosomal damage signals to stress granule formation for cell survival.

Duran, Jacob / Poolsup, Suttinee / Allers, Lee / Lemus, Monica Rosas / Cheng, Qiuying / Pu, Jing / Salemi, Michelle / Phinney, Brett / Jia, Jingyue

bioRxiv : the preprint server for biology

2024

Abstract: Lysosomal damage poses a significant threat to cell survival. Our previous work has reported that lysosomal damage induces stress granule (SG) formation. However, the importance of SG formation in determining cell fate and the precise mechanisms through ... ...

Abstract	Lysosomal damage poses a significant threat to cell survival. Our previous work has reported that lysosomal damage induces stress granule (SG) formation. However, the importance of SG formation in determining cell fate and the precise mechanisms through which lysosomal damage triggers SG formation remains unclear. Here, we show that SG formation is initiated via a novel calcium-dependent pathway and plays a protective role in promoting cell survival in response to lysosomal damage. Mechanistically, we demonstrate that during lysosomal damage, ALIX, a calcium-activated protein, transduces lysosomal damage signals by sensing calcium leakage to induce SG formation by controlling the phosphorylation of eIF2α. ALIX modulates eIF2α phosphorylation by regulating the association between PKR and its activator PACT, with galectin-3 exerting a negative effect on this process. We also found this regulatory event of SG formation occur on damaged lysosomes. Collectively, these investigations reveal novel insights into the precise regulation of SG formation triggered by lysosomal damage, and shed light on the interaction between damaged lysosomes and SGs. Importantly, SG formation is significant for promoting cell survival in the physiological context of lysosomal damage inflicted by SARS-CoV-2 ORF3a, adenovirus infection, Malaria hemozoin, proteopathic tau as well as environmental hazard silica.
Language	English
Publishing date	2024-04-02
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.03.29.587368
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Article ; Online: Dynamic energy dependency of

Liang, Pingdong / Rosas-Lemus, Mónica / Patel, Dhwani / Fang, Xuan / Tuz, Karina / Juárez, Oscar

The Journal of biological chemistry

2017 Volume 293, Issue 2, Page(s) 510–522

Abstract: Chlamydia ... ...

Abstract	Chlamydia trachomatis
MeSH term(s)	Adenosine Triphosphate/metabolism ; Bacterial Outer Membrane Proteins/metabolism ; Carbonyl Cyanide m-Chlorophenyl Hydrazone/pharmacology ; Chlamydia Infections/prevention & control ; Chlamydia trachomatis/drug effects ; Chlamydia trachomatis/metabolism ; Chlamydia trachomatis/pathogenicity ; Energy Metabolism/genetics ; Energy Metabolism/physiology ; HeLa Cells ; Host-Pathogen Interactions ; Humans ; Sodium/metabolism
Chemical Substances	Bacterial Outer Membrane Proteins ; Carbonyl Cyanide m-Chlorophenyl Hydrazone (555-60-2) ; Adenosine Triphosphate (8L70Q75FXE) ; Sodium (9NEZ333N27)
Language	English
Publishing date	2017-11-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M117.797209
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Article ; Online: Mn

Minasov, George / Rosas-Lemus, Monica / Shuvalova, Ludmilla / Inniss, Nicole L / Brunzelle, Joseph S / Daczkowski, Courtney M / Hoover, Paul / Mesecar, Andrew D / Satchell, Karla J F

Science signaling

2021 Volume 14, Issue 689

Abstract: Capping of viral messenger RNAs is essential for efficient translation, for virus replication, and for preventing detection by the host cell innate response system. The SARS-CoV-2 genome encodes the 2'- ...

Abstract	Capping of viral messenger RNAs is essential for efficient translation, for virus replication, and for preventing detection by the host cell innate response system. The SARS-CoV-2 genome encodes the 2'-
MeSH term(s)	Amino Acid Sequence ; COVID-19/virology ; Catalytic Domain ; Crystallography, X-Ray ; Humans ; Manganese/metabolism ; Methylation ; Methyltransferases/chemistry ; Methyltransferases/genetics ; Methyltransferases/metabolism ; Models, Molecular ; Nucleic Acid Conformation ; RNA Caps/chemistry ; RNA Caps/genetics ; RNA Caps/metabolism ; RNA Stability ; RNA, Messenger/chemistry ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; RNA, Viral/chemistry ; RNA, Viral/genetics ; RNA, Viral/metabolism ; Recombinant Proteins/chemistry ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism ; S-Adenosylmethionine/chemistry ; S-Adenosylmethionine/metabolism ; SARS-CoV-2/genetics ; SARS-CoV-2/metabolism ; Signal Transduction ; Substrate Specificity ; Viral Nonstructural Proteins/chemistry ; Viral Nonstructural Proteins/genetics ; Viral Nonstructural Proteins/metabolism
Chemical Substances	NSP16 protein, SARS-CoV-2 ; RNA Caps ; RNA, Messenger ; RNA, Viral ; Recombinant Proteins ; Viral Nonstructural Proteins ; Manganese (42Z2K6ZL8P) ; S-Adenosylmethionine (7LP2MPO46S) ; Methyltransferases (EC 2.1.1.-)
Language	English
Publishing date	2021-06-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2417226-1
ISSN	1937-9145 ; 1945-0877
ISSN (online)	1937-9145
ISSN	1945-0877
DOI	10.1126/scisignal.abh2071
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