PDBsum entry 4y72

Transferase

PDB id: 4y72

Contents

Protein chains

292 a.a.

264 a.a.

74 a.a.

Ligands

LZ9

Waters ×368

PDB id:

4y72

Name:

Transferase

Title:

Human cdk1/cyclinb1/cks2 with inhibitor

Structure:

Cyclin-dependent kinase 1. Chain: a. Synonym: cdk1,cell division control protein 2 homolog,cell division protein kinase 1,p34 protein kinase. Engineered: yes. G2/mitotic-specific cyclin-b1. Chain: b. Engineered: yes. Cyclin-dependent kinases regulatory subunit 2.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: cdk1, cdc2, cdc28a, cdkn1, p34cdc2. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9. Gene: ccnb1, ccnb. Expressed in: escherichia coli bl21(de3).

Resolution:

2.30Å R-factor: 0.190 R-free: 0.252

Authors:

N.R.Brown,S.Korolchuk,M.P.Martin,W.Stanley,R.Moukhametzianov, M.E.M.Noble,J.A.Endicott

Key ref:

N.R.Brown et al. (2015). CDK1 structures reveal conserved and unique features of the essential cell cycle CDK. Nat Commun, 6, 6769. PubMed id: 25864384 DOI: 10.1038/ncomms7769

Date:

13-Feb-15 Release date: 12-Aug-15

Protein chain

P06493  (CDK1_HUMAN) -  Cyclin-dependent kinase 1 from Homo sapiens

Seq: 297 a.a.

Struc: 292 a.a.

Protein chain

P14635  (CCNB1_HUMAN) -  G2/mitotic-specific cyclin-B1 from Homo sapiens

Seq: 433 a.a.

Struc: 264 a.a.*

Protein chain

P33552  (CKS2_HUMAN) -  Cyclin-dependent kinases regulatory subunit 2 from Homo sapiens

Seq: 79 a.a.

Struc: 74 a.a.

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class 2: Chain A: 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 A: 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: 10.1038/ncomms7769

Nat Commun 6:6769 (2015)

PubMed id: 25864384

CDK1 structures reveal conserved and unique features of the essential cell cycle CDK.

N.R.Brown, S.Korolchuk, M.P.Martin, W.A.Stanley, R.Moukhametzianov, M.E.Noble, J.A.Endicott.

ABSTRACT

CDK1 is the only essential cell cycle CDK in human cells and is required for successful completion of M-phase. It is the founding member of the CDK family and is conserved across all eukaryotes. Here we report the crystal structures of complexes of CDK1-Cks1 and CDK1-cyclin B-Cks2. These structures confirm the conserved nature of the inactive monomeric CDK fold and its ability to be remodelled by cyclin binding. Relative to CDK2-cyclin A, CDK1-cyclin B is less thermally stable, has a smaller interfacial surface, is more susceptible to activation segment dephosphorylation and shows differences in the substrate sequence features that determine activity. Both CDK1 and CDK2 are potential cancer targets for which selective compounds are required. We also describe the first structure of CDK1 bound to a potent ATP-competitive inhibitor and identify aspects of CDK1 structure and plasticity that might be exploited to develop CDK1-selective inhibitors.