Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTQ8KVI)

• DTT Name: Staphylococcus 30S ribosomal subunit (Stap-coc pbp2)
• Synonyms: Penicillin-binding protein 2; Penicillin-binding protein; Penicillin binding protein PBP 2
• Gene Name: Stap-coc pbp2
• DTT Type: Successful target; [1]
• Related Disease:
  Acne vulgaris [ICD-11: ED80]
  Acute/subacute hepatic failure [ICD-11: DB91]
  Alcoholic liver disease [ICD-11: DB94]
  Amoebiasis [ICD-11: 1A36]
  Bacterial infection [ICD-11: 1A00-1C4Z]
  Bronchitis [ICD-11: CA20]
  Lyme borreliosis [ICD-11: 1C1G]
  Skin and skin-structure infection [ICD-11: 1F28-1G0Z]
• UniProt ID: F4NA87_STAAU
• TTD ID: T72657
• Sequence:
  MTENKGSSQPKKNGNNGGKSNSKKNRNVKRTIIKIIGFMIIAFFVVLLLGILLFAYYAWK
  APAFTEAKLQDPIPAKIYDKNGELVKTLDNGQRHEHVNLKDVPKSMKDAVLATEDNRFYE
  HGALDYKRLFGAIGKNLTGGFGSEGASTLTQQVVKDAFLSQHKSIGRKAQEAYLSYRLEQ
  EYSKDDIFQVYLNKIYYSDGVTGIKAAAKYYFNKDLKDLNLAEEAYLAGLPQVPNNYNIY
  DHPKAAEDRKNTVLYLMHYHKRITDKQWEDAKKIDLKANLVNRTAEERQNIDTNQDSEYN
  SYVNFVKSELMNNKAFKDENLGNVLQSGIKIYTNMDKDVQKTLQNDVDNGSFYKNKDQQV
  GATILDSKTGGLVAISGGRDFKDVVNRNQATDPHPTGSSLKPFLAYGPAIENMKWATNHA
  IQDESSYQVDGSTFRNYDVKSHGTVSIYDALRQSFNIPALKAWQSVKQNAGNDAPKKFAA
  KLGLNYEGDIGPSEVLGGSASEFSPTQLASAFAAIANGGTYNNAHSIQKVVTRDGETIEY
  DHTSHKAMSDYTAYMLAEMLKGTFKPYGSAYGHGVSGVNMGAKTGTGTYGAETYSQYNLP
  DNAAKDVWINGFTPQYTMSVWMGFSKVKQYGENSFVGHSQQEYPQFLYENVMSKISSRDG
  EDFKRPSSVSGSIPSINVSGSQDNNTTNRSTHGGSDTSANSSGTAQSNNNTRSQQSRNSG
  GLTGIFN
• Function: Subunite of bacterial 70s ribosomes. Invovled in protein biosynthesis.
• KEGG Pathway:
  Peptidoglycan biosynthesis (sams00550)
  Metabolic pathways (sams01100)
  beta-Lactam resistance (sams01501)

Molecular Interaction Atlas (MIA) of This DTT

17 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amikacin	DM5PDRB	Bacterial infection	1A00-1C4Z	Approved	[1]
Clomocycline	DM0ZRMQ	Bacterial infection	1A00-1C4Z	Approved	[2]
Demeclocycline	DMZEPFJ	Acne vulgaris	ED80	Approved	[3]
Framycetin	DMF8DNE	Acute liver failure	DB91	Approved	[4], [5]
Kanamycin	DM2DMPO	Bacterial infection	1A00-1C4Z	Approved	[6]
Lymecycline	DMOMLHJ	Bacterial infection	1A00-1C4Z	Approved	[7]
Meclocycline	DMSFQ8I	Bacterial infection	1A00-1C4Z	Approved	[3]
Methacycline	DMAY96V	Bacterial infection	1A00-1C4Z	Approved	[8]
Minocycline	DMVN5OH	Bacterial infection	1A00-1C4Z	Approved	[9]
Netilmicin	DMRD1QK	Bacterial infection	1A00-1C4Z	Approved	[10]
Oxytetracycline	DMOVH1M	Bacterial infection	1A00-1C4Z	Approved	[3]
Paromomycin	DM1AGXN	Intestinal amebiasis	1A36	Approved	[11], [12]
Rolitetracycline	DMBR5Q7	Acne vulgaris	ED80	Approved	[13]
Spectinomycin	DM0MQ35	Bacterial infection	1A00-1C4Z	Approved	[14]
Streptomycin	DME1LQN	Bacterial infection	1A00-1C4Z	Approved	[14], [15]
Tetracycline	DMZA017	Bacterial infection	1A00-1C4Z	Approved	[16]
Tigecycline	DMLE7IO	Skin infection	1F28-1G0Z	Approved	[17]

References

• [1] Bacterial resistance to aminoglycosides and beta-lactams: the Tn1331 transposon paradigm. Front Biosci. 2000 Jan 1;5:D20-9.
• [2] Molecular dynamics simulations of the 30S ribosomal subunit reveal a preferred tetracycline binding site. J Am Chem Soc. 2008 Jan 30;130(4):1114-5.
• [3] Detection of tetracycline resistance genes by PCR methods. Methods Mol Biol. 2004;268:3-13.
• [4] Characterization of a 30S ribosomal subunit assembly intermediate found in Escherichia coli cells growing with neomycin or paromomycin. Arch Microbiol. 2008 May;189(5):441-9.
• [5] Antistaphylococcal activity of gentamicin. Minerva Med. 1975 Dec 8;66(84):4505-26.
• [6] SsrA-mediated protein tagging in the presence of miscoding drugs and its physiological role in Escherichia coli. Genes Cells. 2002 Jul;7(7):629-38.
• [7] Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34.
• [8] Tetracyclines and pulmonary inflammation. Endocr Metab Immune Disord Drug Targets. 2007 Dec;7(4):232-6.
• [9] Functional, biophysical, and structural bases for antibacterial activity of tigecycline. Antimicrob Agents Chemother. 2006 Jun;50(6):2156-66.
• [10] Ribosomal resistance in the gentamicin producer organism Micromonospora purpurea. Antimicrob Agents Chemother. 1982 Aug;22(2):231-6.
• [11] Aminoglycoside association pathways with the 30S ribosomal subunit. J Phys Chem B. 2009 May 21;113(20):7322-30.
• [12] 30S ribosomal subunit assembly is a target for inhibition by aminoglycosides in Escherichia coli. Antimicrob Agents Chemother. 2002 May;46(5):1546-9.
• [13] Reversed-phase high-performance liquid chromatography coupled to ultraviolet and electrospray time-of-flight mass spectrometry on-line detection fo... J Chromatogr A. 2008 Jun 27;1195(1-2):107-16.
• [14] Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics. Nature. 2000 Sep 21;407(6802):340-8.
• [15] The interaction between streptomycin and ribosomal RNA. Biochimie. 1991 Dec;73(12):1431-8.
• [16] The glycylcyclines: a comparative review with the tetracyclines. Drugs. 2004;64(1):63-88.
• [17] Tigecycline: first of a new class of antimicrobial agents. Pharmacotherapy. 2006 Aug;26(8):1099-110.