Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T66040
(Former ID: TTDS00211)
|
|||||
| Target Name |
Bacterial Penicillin binding protein 2 (Bact mrdA)
|
|||||
| Synonyms |
PBP-2
Click to Show/Hide
|
|||||
| Gene Name |
Bact mrdA
|
|||||
| Target Type |
Successful target
|
[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Bacterial infection [ICD-11: 1A00-1C4Z] | |||||
| Function |
Cell wall formation; PBP-2 is responsible for the determination of the rod shape of the cell. It synthesizes cross- linked peptidoglycan from lipid intermediates.
Click to Show/Hide
|
|||||
| UniProt ID | ||||||
| EC Number |
EC 3.4.16.4
|
|||||
| Sequence |
MKLQNSFRDYTAESALFVRRALVAFLGILLLTGVLIANLYNLQIVRFTDYQTRSNENRIK
LVPIAPSRGIIYDRNGIPLALNRTIYQIEMMPEKVDNVQQTLDALRSVVDLTDDDIAAFR KERARSHRFTSIPVKTNLTEVQVARFAVNQYRFPGVEVKGYKRRYYPYGSALTHVIGYVS KINDKDVERLNNDGKLANYAATHDIGKLGIERYYEDVLHGQTGYEEVEVNNRGRVIRQLK EVPPQAGHDIYLTLDLKLQQYIETLLAGSRAAVVVTDPRTGGVLALVSTPSYDPNLFVDG ISSKDYSALLNDPNTPLVNRATQGVYPPASTVKPYVAVSALSAGVITRNTTLFDPGWWQL PGSEKRYRDWKKWGHGRLNVTRSLEESADTFFYQVAYDMGIDRLSEWMGKFGYGHYTGID LAEERSGNMPTREWKQKRFKKPWYQGDTIPVGIGQGYWTATPIQMSKALMILINDGIVKV PHLLMSTAEDGKQVPWVQPHEPPVGDIHSGYWELAKDGMYGVANRPNGTAHKYFASAPYK IAAKSGTAQVFGLKANETYNAHKIAERLRDHKLMTAFAPYNNPQVAVAMILENGGAGPAV GTLMRQILDHIMLGDNNTDLPAENPAVAAAEDH Click to Show/Hide
|
|||||
| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 3 Approved Drugs | + | ||||
| 1 | Amdinocillin | Drug Info | Approved | Bacterial infection | [2] | |
| 2 | Cefepime | Drug Info | Approved | Bacterial infection | [3] | |
| 3 | Imipenem | Drug Info | Approved | Bacterial infection | [4] | |
| Mode of Action | [+] 3 Modes of Action | + | ||||
| Inhibitor | [+] 1 Inhibitor drugs | + | ||||
| 1 | Amdinocillin | Drug Info | [5] | |||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | Cefepime | Drug Info | [6] | |||
| Binder | [+] 1 Binder drugs | + | ||||
| 1 | Imipenem | Drug Info | [1], [7] | |||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: (3~{R},6~{S})-6-(aminomethyl)-4-(1,3-oxazol-5-yl)-3-(sulfooxyamino)-3,6-dihydro-2~{H}-pyridine-1-carboxylic acid | Ligand Info | |||||
| Structure Description | Structural basis for the inhibition of E. coli PBP2 | PDB:6G9S | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [8] |
| PDB Sequence |
NRIKLVPIAP
66 SRGIIYDRNG76 IPLALNRTIY86 QIEMMPEKVD96 NVQQTLDALR106 SVVDLTDDDI 116 AAFRKERARS126 HRFTSIPVKT136 NLTEVQVARF146 AVNQYRFPGV156 EVKGYKRRYY 166 PYGSALTHVI176 GYVSKINDKD186 VERLNNDGKL196 ANYAATHDIG206 KLGIERYYED 216 VLHGQTGYEE226 VEVNNRGRVI236 RQLKEVPPQA246 GHDIYLTLDL256 KLQQYIETLL 266 AGSRAAVVVT276 DPRTGGVLAL286 VSTPSYDPNL296 FVDGISSKDY306 SALLNDPNTP 316 LVNRATQGVY326 PPASTVKPYV336 AVSALSAGVI346 TRNTTLFDPG356 WWQLPGSEKR 366 YRDWKKWGHG376 RLNVTRSLEE386 SADTFFYQVA396 YDMGIDRLSE406 WMGKFGYGHY 416 TGIDLAEERS426 GNMPTREWKQ436 KRFKKPWYQG446 DTIPVGIGQG456 YWTATPIQMS 466 KALMILINDG476 IVKVPHLLMS486 TAEDGKQVPW496 VQPHEPPVGD506 IHSGYWELAK 516 DGMYGVANRP526 NGTAHKYFAS536 APYKIAAKSG546 TAQRDHKLMT575 AFAPYNNPQV 585 AVAMILENGG595 AGPAVGTLMR605 QILDHIML
|
|||||
|
|
||||||
| Ligand Name: [[(3R,6S)-6-carbamoyl-1-formylpiperidin-3-yl]amino] hydrogen sulfate | Ligand Info | |||||
| Structure Description | Structural basis for the inhibition of E. coli PBP2 | PDB:6G9F | ||||
| Method | X-ray diffraction | Resolution | 2.35 Å | Mutation | No | [8] |
| PDB Sequence |
NRIKLVPIAP
66 SRGIIYDRNG76 IPLALNRTIY86 QIEMMPEKVD96 NVQQTLDALR106 SVVDLTDDDI 116 AAFRKERARS126 HRFTSIPVKT136 NLTEVQVARF146 AVNQYRFPGV156 EVKGYKRRYY 166 PYGSALTHVI176 GYVSKINDKD186 VERLNNDGKL196 ANYAATHDIG206 KLGIERYYED 216 VLHGQTGYEE226 VEVNNRGRVI236 RQLKEVPPQA246 GHDIYLTLDL256 KLQQYIETLL 266 AGSRAAVVVT276 DPRTGGVLAL286 VSTPSYDPNL296 FVDGISSKDY306 SALLNDPNTP 316 LVNRATQGVY326 PPASTVKPYV336 AVSALSAGVI346 TRNTTLFDPG356 WWQLPGSEKR 366 YRDWKKWGHG376 RLNVTRSLEE386 SADTFFYQVA396 YDMGIDRLSE406 WMGKFGYGHY 416 TGIDLAEERS426 GNMPTREWKQ436 KRFKKPWYQG446 DTIPVGIGQG456 YWTATPIQMS 466 KALMILINDG476 IVKVPHLLMS486 TAEDGKQVPW496 VQPHEPPVGD506 IHSGYWELAK 516 DGMYGVANRP526 NGTAHKYFAS536 APYKIAAKSG546 TAQLRDHKLM574 TAFAPYNNPQ 584 VAVAMILENG594 GAGPAVGTLM604 RQILDHIML
|
|||||
|
|
||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
|---|---|
|
Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Similarity Proteins
|
|
|
There is no similarity protein (E value < 0.005) for this target
|
| Drug Property Profile of Target | Top | |
|---|---|---|
| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
|
|
||
| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
|
|
||
| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
|
|
||
| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target-Related Models and Studies | Top | |||||
|---|---|---|---|---|---|---|
| Target Validation | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | A comparative trial of imipenem versus ceftazidime in the release of endotoxin and cytokine generation in patients with gram-negative urosepsis. Urosepsis Study Group. J Endotoxin Res. 2000;6(1):25-31. | |||||
| REF 2 | Drug information of Amdinocillin, 2008. eduDrugs. | |||||
| REF 3 | Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. | |||||
| REF 4 | How many modes of action should an antibiotic have Curr Opin Pharmacol. 2008 Oct;8(5):564-73. | |||||
| REF 5 | Growth of Escherichia coli: significance of peptidoglycan degradation during elongation and septation. J Bacteriol. 2008 Jun;190(11):3914-22. | |||||
| REF 6 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. | |||||
| REF 7 | Laboratory data which differentiate meropenem and imipenem. Scand J Infect Dis Suppl. 1995;96:5-10. | |||||
| REF 8 | Structural Basis for E. coli Penicillin Binding Protein (PBP) 2 Inhibition, a Platform for Drug Design. J Med Chem. 2019 May 9;62(9):4742-4754. | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.