In silico analysis of ftsz crystal structures towards a new target for antibiotics

Kusuma, KD; Griffith, R; Harry, EJ; Bottomley, AL; Ung, AT

In silico analysis of ftsz crystal structures towards a new target for antibiotics

Kusuma, KD

Griffith, R Harry, EJ

Bottomley, AL

Ung, AT

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Publication Type:: Journal Article
Citation:: Australian Journal of Chemistry, 2019, 72 (3), pp. 184 - 193
Issue Date:: 2019-01-01

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Field	Value	Language
dc.contributor.author	Kusuma, KD https://orcid.org/0000-0002-4751-8232	en_US
dc.contributor.author	Griffith, R	en_US
dc.contributor.author	Harry, EJ https://orcid.org/0000-0003-0858-9473	en_US
dc.contributor.author	Bottomley, AL https://orcid.org/0000-0003-0255-0869	en_US
dc.contributor.author	Ung, AT https://orcid.org/0000-0002-5665-0702	en_US
dc.date.issued	2019-01-01	en_US
dc.identifier.citation	Australian Journal of Chemistry, 2019, 72 (3), pp. 184 - 193	en_US
dc.identifier.issn	0004-9425	en_US
dc.identifier.uri	http://hdl.handle.net/10453/129687
dc.description.abstract	© 2019 CSIRO. The bacterial cell division protein FtsZ is conserved in most bacteria and essential for viability. There have been concerted efforts in developing inhibitors that target FtsZ as potential antibiotics. Key to this is an in-depth understanding of FtsZ structure at the molecular level across diverse bacterial species to ensure inhibitors have high affinity for the FtsZ target in a variety of clinically relevant pathogens. In this study, we show that FtsZ structures differ in three ways: (1) the H7 helix curvature; (2) the dimensions of the interdomain cleft; and (3) the opening/closing mechanism of the interdomain cleft, whereas no differences were observed in the dimensions of the nucleotide-binding pocket and T7 loop. Molecular dynamics simulation may suggest that there are two possible mechanisms for the process of opening and closing of the interdomain cleft on FtsZ structures. This discovery highlights significant differences between FtsZ structures at the molecular level and this knowledge is vital in assisting the design of potent FtsZ inhibitors.	en_US
dc.relation.ispartof	Australian Journal of Chemistry	en_US
dc.relation.isbasedon	10.1071/CH18347	en_US
dc.subject.classification	General Chemistry	en_US
dc.title	In silico analysis of ftsz crystal structures towards a new target for antibiotics	en_US
dc.type	Journal Article
utslib.citation.volume	3	en_US
utslib.citation.volume	72	en_US
utslib.for	0306 Physical Chemistry (incl. Structural)	en_US
utslib.for	03 Chemical Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CCET - Centre for Clean Energy Technology
pubs.organisational-group	/University of Technology Sydney/Strength - ithree - Institute of Infection, Immunity and Innovation
utslib.copyright.status	closed_access
pubs.issue	3	en_US
pubs.publication-status	Published	en_US
pubs.volume	72	en_US

Abstract:

© 2019 CSIRO. The bacterial cell division protein FtsZ is conserved in most bacteria and essential for viability. There have been concerted efforts in developing inhibitors that target FtsZ as potential antibiotics. Key to this is an in-depth understanding of FtsZ structure at the molecular level across diverse bacterial species to ensure inhibitors have high affinity for the FtsZ target in a variety of clinically relevant pathogens. In this study, we show that FtsZ structures differ in three ways: (1) the H7 helix curvature; (2) the dimensions of the interdomain cleft; and (3) the opening/closing mechanism of the interdomain cleft, whereas no differences were observed in the dimensions of the nucleotide-binding pocket and T7 loop. Molecular dynamics simulation may suggest that there are two possible mechanisms for the process of opening and closing of the interdomain cleft on FtsZ structures. This discovery highlights significant differences between FtsZ structures at the molecular level and this knowledge is vital in assisting the design of potent FtsZ inhibitors.

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http://hdl.handle.net/10453/129687