title: Molecular modeling study of CodX reveals importance of N-terminal and C-terminal domain in the CodWX complex structure of Bacillus subtilis.
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 (W(6)W(6)X(6)) 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.
authors.affiliation: Department of Biochemistry, Division of Applied Life Sciences, BK21 Program, Environmental Biotechnology National Core Research Center, Gyeongsang National University, Jinju, Republic of Korea.
authors.forename: Navaneethakrishnan
authors.initials: N
authors.lastname: Krishnamoorthy
authors.forename: Poornima
authors.initials: P
authors.lastname: Gajendrarao
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Eom
authors.forename: Yong Jung
authors.initials: YJ
authors.lastname: Kwon
authors.forename: Gang-Won
authors.initials: GW
authors.lastname: Cheong
authors.forename: Keun Woo
authors.initials: KW
authors.lastname: Lee
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000737:chemistry; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry*; D003198:Computer Simulation; D017124:Conserved Sequence; D004926:Escherichia coli / Q000201:enzymology; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018583:Pliability; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D015203:Reproducibility of Results; D016415:Sequence Alignment; D055672:Static Electricity; D040681:Structural Homology, Protein; D013329:Structure-Activity Relationship; D013499:Surface Properties
chemical_list: D001426:Bacterial Proteins; D000244:Adenosine Diphosphate; D000251:Adenosine Triphosphatases