PDBsum entry 6vjs

Transcription

PDB id: 6vjs

Contents

Protein chains

234 a.a.

301 a.a.

1336 a.a.

1164 a.a.

90 a.a.

76 a.a.

471 a.a.

Ligands

QZY

Metals

_MG ×2

_ZN ×4

PDB id:

6vjs

Name:

Transcription

Title:

Escherichia coli RNA polymerase and ureidothiophene-2-carboxylic acid complex

Structure:

DNA-directed RNA polymerase subunit alpha. Chain: a, b, f, g. Synonym: rnap subunit alpha,RNA polymerase subunit alpha, transcriptase subunit alpha. Engineered: yes. DNA-directed RNA polymerase subunit beta. Chain: c, h. Synonym: rnap subunit beta,RNA polymerase subunit beta,transcriptase subunit beta.

Source:

Escherichia coli. Organism_taxid: 562. Gene: rpoa, pez, phs, sez, b3295, jw3257. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: rpob, z5560, ecs4910. Gene: rpoc, tabb, b3988, jw3951. Gene: rpoz, z5075, ecs4524. Gene: rpod.

Resolution:

4.02Å R-factor: 0.231 R-free: 0.276

Authors:

K.S.Murakami,V.Molodtsov

Key ref:

J.Haupenthal et al. (2020). Evaluation of Bacterial RNA Polymerase Inhibitors in a Staphylococcus aureus-Based Wound Infection Model in SKH1 Mice. ACS Infect Dis, 6, 2573-2581. PubMed id: 32886885 DOI: 10.1021/acsinfecdis.0c00034

Date:

17-Jan-20 Release date: 07-Oct-20

Protein chains

P0A7Z4  (RPOA_ECOLI) -  DNA-directed RNA polymerase subunit alpha from Escherichia coli (strain K12)

Seq: 329 a.a.

Struc: 234 a.a.

Protein chain

P0A7Z4  (RPOA_ECOLI) -  DNA-directed RNA polymerase subunit alpha from Escherichia coli (strain K12)

Seq: 329 a.a.

Struc: 301 a.a.

Protein chains

P0A8V2  (RPOB_ECOLI) -  DNA-directed RNA polymerase subunit beta from Escherichia coli (strain K12)

Seq: 1342 a.a.

Struc: 1336 a.a.

Protein chains

P0A8T7  (RPOC_ECOLI) -  DNA-directed RNA polymerase subunit beta' from Escherichia coli (strain K12)

Seq: 1407 a.a.

Struc: 1164 a.a.

Protein chain

P0A800  (RPOZ_ECOLI) -  DNA-directed RNA polymerase subunit omega from Escherichia coli (strain K12)

Seq: 91 a.a.

Struc: 90 a.a.

Protein chain

P0A800  (RPOZ_ECOLI) -  DNA-directed RNA polymerase subunit omega from Escherichia coli (strain K12)

Seq: 91 a.a.

Struc: 76 a.a.

Protein chains

P00579  (RPOD_ECOLI) -  RNA polymerase sigma factor RpoD from Escherichia coli (strain K12)

Seq: 613 a.a.

Struc: 471 a.a.

Enzyme reactions

• Enzyme class 2: Chains A, B, C, D, E, F, G, H, I, J: E.C.2.7.7.6 - DNA-directed Rna polymerase.
• Reaction: RNA(n) + a ribonucleoside 5'-triphosphate = RNA(n+1) + diphosphate
• Enzyme class 3: Chains X, Y: E.C.?

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1021/acsinfecdis.0c00034

ACS Infect Dis 6:2573-2581 (2020)

PubMed id: 32886885

Evaluation of Bacterial RNA Polymerase Inhibitors in a Staphylococcus aureus-Based Wound Infection Model in SKH1 Mice.

J.Haupenthal, Y.Kautz, W.A.M.Elgaher, L.Pätzold, T.Röhrig, M.W.Laschke, T.Tschernig, A.K.H.Hirsch, V.Molodtsov, K.S.Murakami, R.W.Hartmann, M.Bischoff.

ABSTRACT

Chronic wounds infected with pathogens such as Staphylococcus aureus represent a worldwide health concern, especially in patients with a compromised immune system. As antimicrobial resistance has become an immense global problem, novel antibiotics are urgently needed. One strategy to overcome this threatening situation is the search for drugs targeting novel binding sites on essential and validated enzymes such as the bacterial RNA polymerase (RNAP). In this work, we describe the establishment of an in vivo wound infection model based on the pathogen S. aureus and hairless Crl:SKH1-Hrhr (SKH1) mice. The model proved to be a valuable preclinical tool to study selected RNAP inhibitors after topical application. While rifampicin showed a reduction in the loss of body weight induced by the bacteria, an acceleration of wound healing kinetics, and a reduced number of colony forming units in the wound, the ureidothiophene-2-carboxylic acid 1 was inactive under in vivo conditions, probably due to strong plasma protein binding. The cocrystal structure of compound 1 with RNAP, that we hereby also present, will be of great value for applying appropriate structural modifications to further optimize the compound, especially in terms of plasma protein binding.