PDBsum entry 2bkz

Transferase

PDB id

2bkz

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Contents

			Protein chains

					302 a.a. *


					257 a.a. *

			Ligands

					SBC ×2


					SO4 ×2

			Waters ×272

* Residue conservation analysis

PDB id:

2bkz

Links

Name:

Transferase

Title:

Structure of cdk2-cyclin a with pha-404611

Structure:

Cell division protein kinase 2. Chain: a, c. Synonym: p33 protein kinase. Engineered: yes. Cyclin a2. Chain: b, d. Fragment: residues 174-432 (c-terminal portion). Synonym: cyclin a. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Expression_system_cell_line: high five. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.

Biol. unit:

Dimer (from PDB file)

Resolution:

2.60Å

R-factor:

0.230

R-free:

0.259

Authors:

R.Dalessio,A.Bargiottia,S.Metz,M.G.Brasca,A.Cameron,A.Ermoli, A.Marsiglio,P.Polucci,F.Roletto,M.Tibolla,M.L.Vazquez,A.Vulpetti, P.Pevarello

Key ref:

R.D'Alessio et al. (2005). Benzodipyrazoles: a new class of potent CDK2 inhibitors. Bioorg Med Chem Lett, 15, 1315-1319. PubMed id: 15713378 DOI: 10.1016/j.bmcl.2005.01.023

Date:

23-Feb-05

Release date:

08-Mar-06

PROCHECK

	Headers

	References

Protein chains

P24941 (CDK2_HUMAN) - Cyclin-dependent kinase 2 from Homo sapiens

Seq: Struc:					298 a.a. 302 a.a.

Protein chains

P20248 (CCNA2_HUMAN) - Cyclin-A2 from Homo sapiens

Seq: Struc:					432 a.a. 257 a.a.

Key:

PfamA domain

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class 1:

Chains A, C: E.C.2.7.11.22 - cyclin-dependent kinase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

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⁺

L-seryl-[protein]	+	ATP	=	O-phospho-L-seryl-[protein]	+	ADP	+	H(+)

L-threonyl-[protein]	+	ATP	=	O-phospho-L-threonyl-[protein]	+	ADP	+	H(+)

Enzyme class 2:

Chains B, D: E.C.?

[IntEnz] [ExPASy] [KEGG] [BRENDA]

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.bmcl.2005.01.023	Bioorg Med Chem Lett 15:1315-1319 (2005)
PubMed id: 15713378

Benzodipyrazoles: a new class of potent CDK2 inhibitors.
R.D'Alessio, A.Bargiotti, S.Metz, M.G.Brasca, A.Cameron, A.Ermoli, A.Marsiglio, P.Polucci, F.Roletto, M.Tibolla, M.L.Vazquez, A.Vulpetti, P.Pevarello.

ABSTRACT

The synthesis and the preliminary expansion of this new class of CDK2 inhibitors are presented. The synthesis was accomplished using a solution-phase protocol amenable to rapid parallel expansion and suitable to be scaled-up in view of possible lead development. Following a medicinal chemistry program aimed at improving cell permeability and selectivity, a series of compounds with nanomolar activity in the biochemical assay and able to efficiently inhibit tumor cell proliferation has been obtained.

Literature references that cite this PDB file's key reference

PubMed id

Reference

17571187

F.Marchetti, K.L.Sayle, J.Bentley, W.Clegg, N.J.Curtin, J.A.Endicott, B.T.Golding, R.J.Griffin, K.Haggerty, R.W.Harrington, V.Mesguiche, D.R.Newell, M.E.Noble, R.J.Parsons, D.J.Pratt, L.Z.Wang, and I.R.Hardcastle (2007).
Structure-based design of 2-arylamino-4-cyclohexylmethoxy-5-nitroso-6-aminopyrimidine inhibitors of cyclin-dependent kinase 2.

Org Biomol Chem, 5, 1577-1585.

17450625

M.G.Brasca, C.Albanese, R.Amici, D.Ballinari, L.Corti, V.Croci, D.Fancelli, F.Fiorentini, M.Nesi, P.Orsini, F.Orzi, W.Pastori, E.Perrone, E.Pesenti, P.Pevarello, F.Riccardi-Sirtori, F.Roletto, P.Roussel, M.Varasi, A.Vulpetti, and C.Mercurio (2007).
6-Substituted Pyrrolo[3,4-c]pyrazoles: An Improved Class of CDK2 Inhibitors.

ChemMedChem, 2, 841-852.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.