PDBsum entry 3m4o

Transferase/DNA-RNA hybrid

PDB id: 3m4o

Contents

Protein chains

1395 a.a. *

1106 a.a. *

266 a.a. *

214 a.a. *

84 a.a. *

133 a.a. *

119 a.a. *

65 a.a. *

114 a.a. *

46 a.a. *

DNA/RNA

Ligands

C7P

Metals

_MG

_ZN ×8

* Residue conservation analysis

PDB id:

3m4o

Name:

Transferase/DNA-RNA hybrid

Title:

RNA polymerase ii elongation complex b

Structure:

DNA-directed RNA polymerase ii subunit rpb1. Chain: a. Synonym: RNA polymerase ii subunit b1, RNA polymerase ii subunit 1, DNA-directed RNA polymerase iii largest subunit, RNA polymerase ii subunit b220. DNA-directed RNA polymerase ii subunit rpb2. Chain: b. Synonym: RNA polymerase ii subunit 2, DNA-directed RNA polymerase ii 140 kda polypeptide, b150.

Source:

Saccharomyces cerevisiae. Brewer's yeast,lager beer yeast,yeast. Organism_taxid: 4932. Synthetic: yes. Synthetic: yes

Resolution:

3.57Å R-factor: 0.244 R-free: 0.292

Authors:

D.Wang,G.Zhu,X.Huang,S.J.Lippard

Key ref:

D.Wang et al. (2010). X-ray structure and mechanism of RNA polymerase II stalled at an antineoplastic monofunctional platinum-DNA adduct. Proc Natl Acad Sci U S A, 107, 9584-9589. PubMed id: 20448203

Date:

11-Mar-10 Release date: 12-May-10

Protein chain

P04050  (RPB1_YEAST) -  DNA-directed RNA polymerase II subunit RPB1 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 1733 a.a.

Struc: 1395 a.a.

Protein chain

P08518  (RPB2_YEAST) -  DNA-directed RNA polymerase II subunit RPB2 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 1224 a.a.

Struc: 1106 a.a.

Protein chain

P16370  (RPB3_YEAST) -  DNA-directed RNA polymerase II subunit RPB3 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 318 a.a.

Struc: 266 a.a.

Protein chain

P20434  (RPAB1_YEAST) -  DNA-directed RNA polymerases I, II, and III subunit RPABC1 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 215 a.a.

Struc: 214 a.a.

Protein chain

P20435  (RPAB2_YEAST) -  DNA-directed RNA polymerases I, II, and III subunit RPABC2 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 155 a.a.

Struc: 84 a.a.

Protein chain

P20436  (RPAB3_YEAST) -  DNA-directed RNA polymerases I, II, and III subunit RPABC3 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 146 a.a.

Struc: 133 a.a.

Protein chain

P27999  (RPB9_YEAST) -  DNA-directed RNA polymerase II subunit RPB9 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 122 a.a.

Struc: 119 a.a.

Protein chain

P22139  (RPAB5_YEAST) -  DNA-directed RNA polymerases I, II, and III subunit RPABC5 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 70 a.a.

Struc: 65 a.a.

Protein chain

P38902  (RPB11_YEAST) -  DNA-directed RNA polymerase II subunit RPB11 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 120 a.a.

Struc: 114 a.a.

Protein chain

P40422  (RPAB4_YEAST) -  DNA-directed RNA polymerases I, II, and III subunit RPABC4 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 70 a.a.

Struc: 46 a.a.

DNA/RNA chains

A-U-G-G-A-G-A-G-G-A 10 bases

C-T-A-C-C-C-A-T-A-A-C-C-A-C-C-C-C-G-T-C-C-T-C-T-C-C-A-T 28 bases

G-T-G-G-T-T-A-T-G-G-G-T-A-G 14 bases

Enzyme reactions

• Enzyme class: Chains A, B: E.C.2.7.7.6 - DNA-directed Rna polymerase.
• Reaction: RNA(n) + a ribonucleoside 5'-triphosphate = RNA(n+1) + diphosphate

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

Added reference

Proc Natl Acad Sci U S A 107:9584-9589 (2010)

PubMed id: 20448203

X-ray structure and mechanism of RNA polymerase II stalled at an antineoplastic monofunctional platinum-DNA adduct.

D.Wang, G.Zhu, X.Huang, S.J.Lippard.

ABSTRACT

DNA is a major target of anticancer drugs. The resulting adducts interfere with key cellular processes, such as transcription, to trigger downstream events responsible for drug activity. cis-Diammine(pyridine)chloroplatinum(II), cDPCP or pyriplatin, is a monofunctional platinum(II) analogue of the widely used anticancer drug cisplatin having significant anticancer properties with a different spectrum of activity. Its novel structure-activity properties hold promise for overcoming drug resistance and improving the spectrum of treatable cancers over those responsive to cisplatin. However, the detailed molecular mechanism by which cells process DNA modified by pyriplatin and related monofunctional complexes is not at all understood. Here we report the structure of a transcribing RNA polymerase II (pol II) complex stalled at a site-specific monofunctional pyriplatin-DNA adduct in the active site. The results reveal a molecular mechanism of pol II transcription inhibition and drug action that is dramatically different from transcription inhibition by cisplatin and UV-induced 1,2-intrastrand cross-links. Our findings provide insight into structure-activity relationships that may apply to the entire family of monofunctional DNA-damaging agents and pave the way for rational improvement of monofunctional platinum anticancer drugs.