Sometimes less is more-the impact of the number of His residues on the stability of Zn()-SmtB and BigR4 α-5 domain complexes
The increasing number of antibiotic-resistant pathogens has become one of the major health problems of modern times, including infections caused by Mycobacterium tuberculosis . One of the possible mammalian immune system responses to mycobacterial infection is the increase of the zinc( ii ) concentr...
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| Veröffentlicht in: | Dalton transactions : an international journal of inorganic chemistry 2021-09, Vol.5 (35), p.12118-12129 |
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| creator | Rola, Anna Wieczorek, Robert Koz owski, Henryk Krzywoszy ska, Karolina Potocki, S awomir |
| description | The increasing number of antibiotic-resistant pathogens has become one of the major health problems of modern times, including infections caused by
Mycobacterium tuberculosis
. One of the possible mammalian immune system responses to mycobacterial infection is the increase of the zinc(
ii
) concentration in phagosomes to a toxic level. The mycobacterial SmtB protein belongs to the family of ArsR/SmtB transcription regulators. In the presence of high concentrations of metals, SmtB dissociates from DNA and activates the expression of metal efflux proteins. In this work, we focus on the α5 zinc(
ii
) binding domains of SmtB/BigR4 proteins (the latter being the SmtB homolog from non-pathogenic
M. smegmatis
) and two mutants of BigR4. We will be taking a closer look at the coordination modes and thermodynamic properties of their zinc(
ii
) complexes. The study points out the specificity of metal-ligand interactions and describes the effect of mutations on the coordination properties of the studied systems. The stabilities of the zinc(
ii
) complexes were determined by potentiometry. The coordination sites were determined by NMR experiments and DFT calculations. The comparison of complex stabilities reveals that the Zn(
ii
)-BigR4 species are more stable than the Zn(
ii
)-SmtB complexes. His mutations strongly affect the stability of the complexes and the coordination modes of the metal ion. Exchanging one of the histidines for alanine causes, surprisingly, an increase in the stability of zinc(
ii
) complexes with the studied domain. This was confirmed by potentiometric and DFT methods. This work can be considered as a bioinorganic introduction to the discovery of new strategies in
M. tuberculosis
infection treatment based on zinc(
ii
)-sensitive mechanisms.
The formation equilibria of zinc(
ii
) complexes of the α5 binding domain of SmtB/BigR4 proteins and mutants of the latter are studied and an unusual behaviour of histidine ligands is observed. |
| doi_str_mv | 10.1039/d1dt01690c |
| format | Article |
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Mycobacterium tuberculosis
. One of the possible mammalian immune system responses to mycobacterial infection is the increase of the zinc(
ii
) concentration in phagosomes to a toxic level. The mycobacterial SmtB protein belongs to the family of ArsR/SmtB transcription regulators. In the presence of high concentrations of metals, SmtB dissociates from DNA and activates the expression of metal efflux proteins. In this work, we focus on the α5 zinc(
ii
) binding domains of SmtB/BigR4 proteins (the latter being the SmtB homolog from non-pathogenic
M. smegmatis
) and two mutants of BigR4. We will be taking a closer look at the coordination modes and thermodynamic properties of their zinc(
ii
) complexes. The study points out the specificity of metal-ligand interactions and describes the effect of mutations on the coordination properties of the studied systems. The stabilities of the zinc(
ii
) complexes were determined by potentiometry. The coordination sites were determined by NMR experiments and DFT calculations. The comparison of complex stabilities reveals that the Zn(
ii
)-BigR4 species are more stable than the Zn(
ii
)-SmtB complexes. His mutations strongly affect the stability of the complexes and the coordination modes of the metal ion. Exchanging one of the histidines for alanine causes, surprisingly, an increase in the stability of zinc(
ii
) complexes with the studied domain. This was confirmed by potentiometric and DFT methods. This work can be considered as a bioinorganic introduction to the discovery of new strategies in
M. tuberculosis
infection treatment based on zinc(
ii
)-sensitive mechanisms.
The formation equilibria of zinc(
ii
) complexes of the α5 binding domain of SmtB/BigR4 proteins and mutants of the latter are studied and an unusual behaviour of histidine ligands is observed.</description><identifier>ISSN: 1477-9226</identifier><identifier>EISSN: 1477-9234</identifier><identifier>DOI: 10.1039/d1dt01690c</identifier><language>eng</language><publisher>Cambridge: Royal Society of Chemistry</publisher><subject>Alanine ; Antibiotics ; Coordination compounds ; Efflux ; Electrical measurement ; Gene expression ; Homology ; Immune system ; Mutation ; NMR ; Nuclear magnetic resonance ; Potentiometric analysis ; Proteins ; Stability ; Thermodynamic properties ; Tuberculosis ; Zinc ; Zinc compounds</subject><ispartof>Dalton transactions : an international journal of inorganic chemistry, 2021-09, Vol.5 (35), p.12118-12129</ispartof><rights>Copyright Royal Society of Chemistry 2021</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c273t-aa62b459f9d1ff024d18a855bd820075ec9f327f8faa33cc6b350e591ab3113</cites><orcidid>0000-0002-5528-7200</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>Rola, Anna</creatorcontrib><creatorcontrib>Wieczorek, Robert</creatorcontrib><creatorcontrib>Koz owski, Henryk</creatorcontrib><creatorcontrib>Krzywoszy ska, Karolina</creatorcontrib><creatorcontrib>Potocki, S awomir</creatorcontrib><title>Sometimes less is more-the impact of the number of His residues on the stability of Zn()-SmtB and BigR4 α-5 domain complexes</title><title>Dalton transactions : an international journal of inorganic chemistry</title><description>The increasing number of antibiotic-resistant pathogens has become one of the major health problems of modern times, including infections caused by
Mycobacterium tuberculosis
. One of the possible mammalian immune system responses to mycobacterial infection is the increase of the zinc(
ii
) concentration in phagosomes to a toxic level. The mycobacterial SmtB protein belongs to the family of ArsR/SmtB transcription regulators. In the presence of high concentrations of metals, SmtB dissociates from DNA and activates the expression of metal efflux proteins. In this work, we focus on the α5 zinc(
ii
) binding domains of SmtB/BigR4 proteins (the latter being the SmtB homolog from non-pathogenic
M. smegmatis
) and two mutants of BigR4. We will be taking a closer look at the coordination modes and thermodynamic properties of their zinc(
ii
) complexes. The study points out the specificity of metal-ligand interactions and describes the effect of mutations on the coordination properties of the studied systems. The stabilities of the zinc(
ii
) complexes were determined by potentiometry. The coordination sites were determined by NMR experiments and DFT calculations. The comparison of complex stabilities reveals that the Zn(
ii
)-BigR4 species are more stable than the Zn(
ii
)-SmtB complexes. His mutations strongly affect the stability of the complexes and the coordination modes of the metal ion. Exchanging one of the histidines for alanine causes, surprisingly, an increase in the stability of zinc(
ii
) complexes with the studied domain. This was confirmed by potentiometric and DFT methods. This work can be considered as a bioinorganic introduction to the discovery of new strategies in
M. tuberculosis
infection treatment based on zinc(
ii
)-sensitive mechanisms.
The formation equilibria of zinc(
ii
) complexes of the α5 binding domain of SmtB/BigR4 proteins and mutants of the latter are studied and an unusual behaviour of histidine ligands is observed.</description><subject>Alanine</subject><subject>Antibiotics</subject><subject>Coordination compounds</subject><subject>Efflux</subject><subject>Electrical measurement</subject><subject>Gene expression</subject><subject>Homology</subject><subject>Immune system</subject><subject>Mutation</subject><subject>NMR</subject><subject>Nuclear magnetic resonance</subject><subject>Potentiometric analysis</subject><subject>Proteins</subject><subject>Stability</subject><subject>Thermodynamic properties</subject><subject>Tuberculosis</subject><subject>Zinc</subject><subject>Zinc compounds</subject><issn>1477-9226</issn><issn>1477-9234</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNpFkMtKAzEUhoMoWKsb90LAjQqjuUzmsrStNygItis3QyYXTZlMapKCXfhQvojP5EwrdXXOz_nO-Q8_AKcYXWNEyxuJZUQ4K5HYAwOc5nlSEpru73qSHYKjEBYIEYIYGYCvmbMqGqsCbFQI0ARonVdJfFfQ2CUXEToNe9WubK18rx47yKtg5Krbcu1mGiKvTWPiugde24vLZGbjCPJWwpF5e0nhz3fCoHSWmxYKZ5eN-lThGBxo3gR18leHYHZ_Nx8_JtPnh6fx7TQRJKcx4TwjdcpKXUqsNSKpxAUvGKtlQRDKmRKlpiTXheacUiGymjKkWIl5TTGmQ3C-vbr07qP7OVYLt_JtZ1gRlhNcEFrkHXW1pYR3IXilq6U3lvt1hVHVh1tN8GS-CXfcwWdb2Aex4_7Dp79Ul3Zo</recordid><startdate>20210914</startdate><enddate>20210914</enddate><creator>Rola, Anna</creator><creator>Wieczorek, Robert</creator><creator>Koz owski, Henryk</creator><creator>Krzywoszy ska, Karolina</creator><creator>Potocki, S awomir</creator><general>Royal Society of Chemistry</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>L7M</scope><orcidid>https://orcid.org/0000-0002-5528-7200</orcidid></search><sort><creationdate>20210914</creationdate><title>Sometimes less is more-the impact of the number of His residues on the stability of Zn()-SmtB and BigR4 α-5 domain complexes</title><author>Rola, Anna ; Wieczorek, Robert ; Koz owski, Henryk ; Krzywoszy ska, Karolina ; Potocki, S awomir</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c273t-aa62b459f9d1ff024d18a855bd820075ec9f327f8faa33cc6b350e591ab3113</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Alanine</topic><topic>Antibiotics</topic><topic>Coordination compounds</topic><topic>Efflux</topic><topic>Electrical measurement</topic><topic>Gene expression</topic><topic>Homology</topic><topic>Immune system</topic><topic>Mutation</topic><topic>NMR</topic><topic>Nuclear magnetic resonance</topic><topic>Potentiometric analysis</topic><topic>Proteins</topic><topic>Stability</topic><topic>Thermodynamic properties</topic><topic>Tuberculosis</topic><topic>Zinc</topic><topic>Zinc compounds</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rola, Anna</creatorcontrib><creatorcontrib>Wieczorek, Robert</creatorcontrib><creatorcontrib>Koz owski, Henryk</creatorcontrib><creatorcontrib>Krzywoszy ska, Karolina</creatorcontrib><creatorcontrib>Potocki, S awomir</creatorcontrib><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><jtitle>Dalton transactions : an international journal of inorganic chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rola, Anna</au><au>Wieczorek, Robert</au><au>Koz owski, Henryk</au><au>Krzywoszy ska, Karolina</au><au>Potocki, S awomir</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sometimes less is more-the impact of the number of His residues on the stability of Zn()-SmtB and BigR4 α-5 domain complexes</atitle><jtitle>Dalton transactions : an international journal of inorganic chemistry</jtitle><date>2021-09-14</date><risdate>2021</risdate><volume>5</volume><issue>35</issue><spage>12118</spage><epage>12129</epage><pages>12118-12129</pages><issn>1477-9226</issn><eissn>1477-9234</eissn><abstract>The increasing number of antibiotic-resistant pathogens has become one of the major health problems of modern times, including infections caused by
Mycobacterium tuberculosis
. One of the possible mammalian immune system responses to mycobacterial infection is the increase of the zinc(
ii
) concentration in phagosomes to a toxic level. The mycobacterial SmtB protein belongs to the family of ArsR/SmtB transcription regulators. In the presence of high concentrations of metals, SmtB dissociates from DNA and activates the expression of metal efflux proteins. In this work, we focus on the α5 zinc(
ii
) binding domains of SmtB/BigR4 proteins (the latter being the SmtB homolog from non-pathogenic
M. smegmatis
) and two mutants of BigR4. We will be taking a closer look at the coordination modes and thermodynamic properties of their zinc(
ii
) complexes. The study points out the specificity of metal-ligand interactions and describes the effect of mutations on the coordination properties of the studied systems. The stabilities of the zinc(
ii
) complexes were determined by potentiometry. The coordination sites were determined by NMR experiments and DFT calculations. The comparison of complex stabilities reveals that the Zn(
ii
)-BigR4 species are more stable than the Zn(
ii
)-SmtB complexes. His mutations strongly affect the stability of the complexes and the coordination modes of the metal ion. Exchanging one of the histidines for alanine causes, surprisingly, an increase in the stability of zinc(
ii
) complexes with the studied domain. This was confirmed by potentiometric and DFT methods. This work can be considered as a bioinorganic introduction to the discovery of new strategies in
M. tuberculosis
infection treatment based on zinc(
ii
)-sensitive mechanisms.
The formation equilibria of zinc(
ii
) complexes of the α5 binding domain of SmtB/BigR4 proteins and mutants of the latter are studied and an unusual behaviour of histidine ligands is observed.</abstract><cop>Cambridge</cop><pub>Royal Society of Chemistry</pub><doi>10.1039/d1dt01690c</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-5528-7200</orcidid></addata></record> |
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| source | Royal Society Of Chemistry Journals; Alma/SFX Local Collection |
| subjects | Alanine Antibiotics Coordination compounds Efflux Electrical measurement Gene expression Homology Immune system Mutation NMR Nuclear magnetic resonance Potentiometric analysis Proteins Stability Thermodynamic properties Tuberculosis Zinc Zinc compounds |
| title | Sometimes less is more-the impact of the number of His residues on the stability of Zn()-SmtB and BigR4 α-5 domain complexes |
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