PDBsum entry 7b5o

Transcription

PDB id: 7b5o

Contents

Protein chains

65 a.a.

281 a.a.

297 a.a.

Ligands

I74

Waters ×73

PDB id:

7b5o

Name:

Transcription

Title:

Cryo-em structure of the human cak bound to icec0942 at 2.5 angstroms resolution

Structure:

Cdk-activating kinase assembly factor mat1. Chain: h. Synonym: cdk7/cyclin-h assembly factor,cyclin-g1-interacting protein, menage a trois,ring finger protein 66,ring finger protein mat1,p35, p36. Engineered: yes. Cyclin-h. Chain: i. Synonym: mo15-associated protein,p34,p37.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: mnat1, cap35, mat1, rnf66. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Expression_system_cell_line: high5. Gene: ccnh. Gene: cdk7, cak, cak1, cdkn7, mo15, stk1.

Authors:

B.J.Greber,J.Remis,S.Ali,E.Nogales

Key ref:

B.J.Greber et al. (2021). 2.5 Å-resolution structure of human CDK-activating kinase bound to the clinical inhibitor ICEC0942. Biophys J, 120, 677-686. PubMed id: 33476598 DOI: 10.1016/j.bpj.2020.12.030

Date:

05-Dec-20 Release date: 10-Feb-21

Protein chain

P51948  (MAT1_HUMAN) -  CDK-activating kinase assembly factor MAT1 from Homo sapiens

Seq: 309 a.a.

Struc: 65 a.a.

Protein chain

P51946  (CCNH_HUMAN) -  Cyclin-H from Homo sapiens

Seq: 323 a.a.

Struc: 281 a.a.

Protein chain

P50613  (CDK7_HUMAN) -  Cyclin-dependent kinase 7 from Homo sapiens

Seq: 346 a.a.

Struc: 297 a.a.

Enzyme reactions

• Enzyme class 1: Chains H, I: E.C.?
• Enzyme class 2: Chain J: E.C.2.7.11.22 - cyclin-dependent kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺
• Enzyme class 3: Chain J: E.C.2.7.11.23 - [RNA-polymerase]-subunit kinase.
• Reaction: [DNA-directed RNA polymerase] + ATP = phospho-[DNA-directed RNA polymerase] + ADP + H⁺

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

reference

DOI no: 10.1016/j.bpj.2020.12.030

Biophys J 120:677-686 (2021)

PubMed id: 33476598

2.5 Å-resolution structure of human CDK-activating kinase bound to the clinical inhibitor ICEC0942.

B.J.Greber, J.Remis, S.Ali, E.Nogales.

ABSTRACT

The human CDK-activating kinase (CAK), composed of CDK7, cyclin H, and MAT1, is involved in the control of transcription initiation and the cell cycle. Because of these activities, it has been identified as a promising target for cancer chemotherapy. A number of CDK7 inhibitors have entered clinical trials, among them ICEC0942 (also known as CT7001). Structural information can aid in improving the affinity and specificity of such drugs or drug candidates, reducing side effects in patients. Here, we have determined the structure of the human CAK in complex with ICEC0942 at 2.5 Å-resolution using cryogenic electron microscopy. Our structure reveals conformational differences of ICEC0942 compared with previous X-ray crystal structures of the CDK2-bound complex, and highlights the critical ability of cryogenic electron microscopy to resolve structures of drug-bound protein complexes without the need to crystalize the protein target.