Molecule Information

General Information of the Molecule (ID: Mol00990)

• Name: Lon protease (LON) ,Pseudomonas aeruginosa
• Synonyms: ATP-dependent protease La; PA0779
• Molecule Type: Protein
• Gene Name: lon
• Gene ID: 877837
• Sequence:
  MSDQDVNPEHISDAQPAGTGLVLPGQTLPTTLYVIPIHNRPFFPAQVLPVIVNEEPWAET
  LELVAKTDHHSLALFFMDNPPEDPRHFDVNSLPEHGTLVRVHHASREGGKLQFVAQGLSR
  VRIRGWIKRHRPPFMVEVDYPKTPIDPSDEVKAYGMALINAIKELLPLNPLYSEELKNYL
  NRFSPNDPSPLTDFAAALTTAPGGELQEVLDTVPILKRMEKVLPLLRKEVEVARLQKELS
  AEVNRKIGEHQREFFLKEQLKIIQQELGITKDDKSADADEFRARLEGKVLPEQARKRIDE
  ELNKLSILESGSPEYAVTRNYLDWATALPWGVYGKDKLDLKHARKVLDKHHAGLDDIKDR
  ILEFLAVGSFKGEIAGSIVLLVGPPGVGKTSIGKSIAESLGRPFYRFSVGGMRDEAEIKG
  HRRTYIGALPGKLVQALKEVEVMNPVIMLDEIDKLGASYQGDPASALLETLDPEQNVEFL
  DHYLDLRLDLSKVLFVCTANTLDSIPGPLLDRMEVIRLSGYISEEKLAIAKRHLWPKQLE
  KAGVPKGRLSISDAALRAVIEGYAREAGVRQLEKQLGKLVRKSVVKLLEDPESKVKIGPR
  DLEDYLGMPVFRSEQVLSGIGVITGLAWTSMGGATLPIEATRIHTLNRGFKLTGQLGDVM
  KESAEIAYSYIGSHLKKYGGDPTFFDQAFVHLHVPEGATPKDGPSAGVTMASALLSLARN
  QVPKKGVAMTGELTLTGQVLPIGGVREKVIAARRQKIFELILPEANRGHFEELPDYLREG
  LTVHFAKRYGDVAKVLFPA
• Function: ATP-dependent serine protease that mediates the selective degradation of mutant and abnormal proteins as well as certain short-lived regulatory proteins. Required for cellular homeostasis and for survival from DNA damage and developmental changes induced by stress. Degrades polypeptides processively to yield small peptide fragments that are 5 to 10 amino acids long. Binds to DNA in a double-stranded, site-specific manner.
• Uniprot ID: Q9I5F9_PSEAE

Kingdom: N.A.
Phylum: Proteobacteria
Class: Gammaproteobacteria
Order: Pseudomonadales
Family: Pseudomonadaceae
Genus: Pseudomonas
Species: Pseudomonas aeruginosa

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Tobramycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Pseudomonas aeruginosa infection [1]

• Resistant Disease: Pseudomonas aeruginosa infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Tobramycin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Pseudomonas aeruginosa MPAO1; 1131757
• Experiment for Molecule Alteration: SRM analysis
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: The extracellular polysaccharide layer of biofilm can prolong the time of bactericide penetration into the central cell cluster. The proteomic response of Pseudomonas aeruginosa depends on the level of tobramycin experienced by the cells after exposure to various sub inhibitory levels (0.1-1) u Tobramycin (g / ml) can induce different proteins. Bacterial cells exposed to low levels of tobramycin showed elevated levels of enzymes that metabolize and synthesize amino acids that may alter drug sensitivity. Inactivation of ibpA did not yield significant tobramycin MIC changes. However, inactivation of two heat shock proteins/proteases ibpA/clpB, ibpA/PA0779, or ibpA/hslV led to increased tobramycin sensitivity changes in P. aeruginosa.

References

• Ref 1: Dynamic Proteome Response of Pseudomonas aeruginosa to Tobramycin Antibiotic Treatment. Mol Cell Proteomics. 2015 Aug;14(8):2126-37. doi: 10.1074/mcp.M115.050161. Epub 2015 May 27.