Molecular modeling study of CodX reveals importance of N-terminal and C-terminal domain in the CodWX complex structure of Bacillus subtilis

Navaneethakrishnan Krishnamoorthy, Poornima Gajendrarao, Soo Hyun Eom, Yong Jung Kwon, Gang Won Cheong, Keun Woo Lee

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

In Bacillus subtilis, CodW peptidase and CodX ATPase function together as a distinctive ATP-dependent protease called CodWX, which participates in protein degradation and regulates cell division. The molecular structure of CodX and the assembly structure of CodW-CodX have not yet been resolved. Here we present the first three-dimensional structure of CodX N-terminal (N) and C-terminal (C) domain including possible structure of intermediate (I) domain based on the crystal structure of homologous Escherichia coli HslU ATPase. Moreover, the biologically relevant CodWX (W6W6X6) octadecamer complex structure was constructed using the recently identified CodW-HslU hybrid crystal structure. Molecular dynamics (MD) simulation shows a reasonably stable structure of modeled CodWX and explicit behavior of key segments in CodX N and C domain: nucleotide binding residues, GYVG pore motif and CodW-CodX interface. Predicted structure of the possible I domain is flexible in nature with highly coiled hydrophobic region (M153-M206) that could favor substrate binding and entry. Electrostatic surface potential observation unveiled charge complementarity based CodW-CodX interaction pattern could be a possible native interaction pattern in the interface of CodWX. CodX GYVG pore motif structural features, flexible nature of glycine (G92 and G95) residues and aromatic ring conformation preserved Y93 indicated that it may follow the similar mode during the proteolysis mechanism as in the HslU closed state. This molecular modeling study uncovers the significance of CodX N and C domain in CodWX complex and provides possible explanations which would be helpful to understand the CodWX-dependent proteolysis mechanism of B. subtilis.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalJournal of Molecular Graphics and Modelling
Volume27
Issue number1
DOIs
Publication statusPublished - 1 Aug 2008
Externally publishedYes

Fingerprint

Proteolysis
Molecular modeling
Bacillus
Bacilli
Adenosine Triphosphatases
ATP-Dependent Proteases
Crystal structure
Adenosinetriphosphate
Surface potential
Nucleotides
Glycine
Escherichia coli
Molecular structure
Conformations
Molecular dynamics
Amino acids
Electrostatics
Peptide Hydrolases
Cells
Proteins

Keywords

  • ATP-dependent protease
  • ATPase
  • CodX
  • Electrostatic potential calculation
  • Homology modeling
  • HslU
  • MD simulation

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Spectroscopy
  • Atomic and Molecular Physics, and Optics

Cite this

Molecular modeling study of CodX reveals importance of N-terminal and C-terminal domain in the CodWX complex structure of Bacillus subtilis. / Krishnamoorthy, Navaneethakrishnan; Gajendrarao, Poornima; Eom, Soo Hyun; Kwon, Yong Jung; Cheong, Gang Won; Lee, Keun Woo.

In: Journal of Molecular Graphics and Modelling, Vol. 27, No. 1, 01.08.2008, p. 1-12.

Research output: Contribution to journalArticle

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abstract = "In Bacillus subtilis, CodW peptidase and CodX ATPase function together as a distinctive ATP-dependent protease called CodWX, which participates in protein degradation and regulates cell division. The molecular structure of CodX and the assembly structure of CodW-CodX have not yet been resolved. Here we present the first three-dimensional structure of CodX N-terminal (N) and C-terminal (C) domain including possible structure of intermediate (I) domain based on the crystal structure of homologous Escherichia coli HslU ATPase. Moreover, the biologically relevant CodWX (W6W6X6) octadecamer complex structure was constructed using the recently identified CodW-HslU hybrid crystal structure. Molecular dynamics (MD) simulation shows a reasonably stable structure of modeled CodWX and explicit behavior of key segments in CodX N and C domain: nucleotide binding residues, GYVG pore motif and CodW-CodX interface. Predicted structure of the possible I domain is flexible in nature with highly coiled hydrophobic region (M153-M206) that could favor substrate binding and entry. Electrostatic surface potential observation unveiled charge complementarity based CodW-CodX interaction pattern could be a possible native interaction pattern in the interface of CodWX. CodX GYVG pore motif structural features, flexible nature of glycine (G92 and G95) residues and aromatic ring conformation preserved Y93 indicated that it may follow the similar mode during the proteolysis mechanism as in the HslU closed state. This molecular modeling study uncovers the significance of CodX N and C domain in CodWX complex and provides possible explanations which would be helpful to understand the CodWX-dependent proteolysis mechanism of B. subtilis.",
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T1 - Molecular modeling study of CodX reveals importance of N-terminal and C-terminal domain in the CodWX complex structure of Bacillus subtilis

AU - Krishnamoorthy, Navaneethakrishnan

AU - Gajendrarao, Poornima

AU - Eom, Soo Hyun

AU - Kwon, Yong Jung

AU - Cheong, Gang Won

AU - Lee, Keun Woo

PY - 2008/8/1

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N2 - In Bacillus subtilis, CodW peptidase and CodX ATPase function together as a distinctive ATP-dependent protease called CodWX, which participates in protein degradation and regulates cell division. The molecular structure of CodX and the assembly structure of CodW-CodX have not yet been resolved. Here we present the first three-dimensional structure of CodX N-terminal (N) and C-terminal (C) domain including possible structure of intermediate (I) domain based on the crystal structure of homologous Escherichia coli HslU ATPase. Moreover, the biologically relevant CodWX (W6W6X6) octadecamer complex structure was constructed using the recently identified CodW-HslU hybrid crystal structure. Molecular dynamics (MD) simulation shows a reasonably stable structure of modeled CodWX and explicit behavior of key segments in CodX N and C domain: nucleotide binding residues, GYVG pore motif and CodW-CodX interface. Predicted structure of the possible I domain is flexible in nature with highly coiled hydrophobic region (M153-M206) that could favor substrate binding and entry. Electrostatic surface potential observation unveiled charge complementarity based CodW-CodX interaction pattern could be a possible native interaction pattern in the interface of CodWX. CodX GYVG pore motif structural features, flexible nature of glycine (G92 and G95) residues and aromatic ring conformation preserved Y93 indicated that it may follow the similar mode during the proteolysis mechanism as in the HslU closed state. This molecular modeling study uncovers the significance of CodX N and C domain in CodWX complex and provides possible explanations which would be helpful to understand the CodWX-dependent proteolysis mechanism of B. subtilis.

AB - In Bacillus subtilis, CodW peptidase and CodX ATPase function together as a distinctive ATP-dependent protease called CodWX, which participates in protein degradation and regulates cell division. The molecular structure of CodX and the assembly structure of CodW-CodX have not yet been resolved. Here we present the first three-dimensional structure of CodX N-terminal (N) and C-terminal (C) domain including possible structure of intermediate (I) domain based on the crystal structure of homologous Escherichia coli HslU ATPase. Moreover, the biologically relevant CodWX (W6W6X6) octadecamer complex structure was constructed using the recently identified CodW-HslU hybrid crystal structure. Molecular dynamics (MD) simulation shows a reasonably stable structure of modeled CodWX and explicit behavior of key segments in CodX N and C domain: nucleotide binding residues, GYVG pore motif and CodW-CodX interface. Predicted structure of the possible I domain is flexible in nature with highly coiled hydrophobic region (M153-M206) that could favor substrate binding and entry. Electrostatic surface potential observation unveiled charge complementarity based CodW-CodX interaction pattern could be a possible native interaction pattern in the interface of CodWX. CodX GYVG pore motif structural features, flexible nature of glycine (G92 and G95) residues and aromatic ring conformation preserved Y93 indicated that it may follow the similar mode during the proteolysis mechanism as in the HslU closed state. This molecular modeling study uncovers the significance of CodX N and C domain in CodWX complex and provides possible explanations which would be helpful to understand the CodWX-dependent proteolysis mechanism of B. subtilis.

KW - ATP-dependent protease

KW - ATPase

KW - CodX

KW - Electrostatic potential calculation

KW - Homology modeling

KW - HslU

KW - MD simulation

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