PDBsum entry 3blq

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protein ligands metals Protein-protein interface(s) links
Transcription PDB id
Protein chains
296 a.a. *
251 a.a. *
Waters ×30
* Residue conservation analysis
PDB id:
Name: Transcription
Title: Crystal structure of human cdk9/cyclint1 in complex with atp
Structure: Cell division protein kinase 9. Chain: a. Fragment: unp residues 2-330. Synonym: cyclin-dependent kinase 9, serine/threonine- protein kinase pitalre, c-2k, cell division cycle 2-like protein kinase 4. Engineered: yes. Cyclin-t1. Chain: b.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: cdk9. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Gene: ccnt1.
2.90Å     R-factor:   0.174     R-free:   0.234
Authors: S.Baumli,G.Lolli,E.D.Lowe,L.N.Johnson
Key ref: S.Baumli et al. (2008). The structure of P-TEFb (CDK9/cyclin T1), its complex with flavopiridol and regulation by phosphorylation. EMBO J, 27, 1907-1918. PubMed id: 18566585 DOI: 10.1038/emboj.2008.121
11-Dec-07     Release date:   01-Jul-08    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P50750  (CDK9_HUMAN) -  Cyclin-dependent kinase 9
372 a.a.
296 a.a.*
Protein chain
Pfam   ArchSchema ?
O60563  (CCNT1_HUMAN) -  Cyclin-T1
726 a.a.
251 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class 2: Chain A: E.C.  - Cyclin-dependent kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
Bound ligand (Het Group name = ATP)
corresponds exactly
+ protein
+ phosphoprotein
   Enzyme class 3: Chain A: E.C.  - [RNA-polymerase]-subunit kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + [DNA-directed RNA polymerase] = ADP + [DNA-directed RNA polymerase] phosphate
Bound ligand (Het Group name = ATP)
corresponds exactly
+ [DNA-directed RNA polymerase]
+ [DNA-directed RNA polymerase] phosphate
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
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     transcription, DNA-dependent   4 terms 
  Biochemical function     transferase activity, transferring phosphorus-containing groups     5 terms  


DOI no: 10.1038/emboj.2008.121 EMBO J 27:1907-1918 (2008)
PubMed id: 18566585  
The structure of P-TEFb (CDK9/cyclin T1), its complex with flavopiridol and regulation by phosphorylation.
S.Baumli, G.Lolli, E.D.Lowe, S.Troiani, L.Rusconi, A.N.Bullock, J.E.Debreczeni, S.Knapp, L.N.Johnson.
The positive transcription elongation factor b (P-TEFb) (CDK9/cyclin T (CycT)) promotes mRNA transcriptional elongation through phosphorylation of elongation repressors and RNA polymerase II. To understand the regulation of a transcriptional CDK by its cognate cyclin, we have determined the structures of the CDK9/CycT1 and free cyclin T2. There are distinct differences between CDK9/CycT1 and the cell cycle CDK CDK2/CycA manifested by a relative rotation of 26 degrees of CycT1 with respect to the CDK, showing for the first time plasticity in CDK cyclin interactions. The CDK9/CycT1 interface is relatively sparse but retains some core CDK-cyclin interactions. The CycT1 C-terminal helix shows flexibility that may be important for the interaction of this region with HIV TAT and HEXIM. Flavopiridol, an anticancer drug in phase II clinical trials, binds to the ATP site of CDK9 inducing unanticipated structural changes that bury the inhibitor. CDK9 activity and recognition of regulatory proteins are governed by autophosphorylation. We show that CDK9/CycT1 autophosphorylates on Thr186 in the activation segment and three C-terminal phosphorylation sites. Autophosphorylation on all sites occurs in cis.

Literature references that cite this PDB file's key reference

  PubMed id Reference
23064645 S.Larochelle, R.Amat, K.Glover-Cutter, M.Sansó, C.Zhang, J.J.Allen, K.M.Shokat, D.L.Bentley, and R.P.Fisher (2012).
Cyclin-dependent kinase control of the initiation-to-elongation switch of RNA polymerase II.
  Nat Struct Mol Biol, 19, 1108-1115.  
21333571 C.Fang, Z.Xiao, and Z.Guo (2011).
Generation and validation of the first predictive pharmacophore model for cyclin-dependent kinase 9 inhibitors.
  J Mol Graph Model, 29, 800-808.  
21429632 H.M.Shallal, and W.A.Russu (2011).
Discovery, synthesis, and investigation of the antitumor activity of novel piperazinylpyrimidine derivatives.
  Eur J Med Chem, 46, 2043-2057.  
21038395 D.Myatt, L.Johnson, S.Baumli, and G.Siligardi (2010).
The binding of flavopiridol to blood serum albumin.
  Chirality, 22, E40-E43.  
  20201073 E.C.Dow, H.Liu, and A.P.Rice (2010).
T-loop phosphorylated Cdk9 localizes to nuclear speckle domains which may serve as sites of active P-TEFb function and exchange between the Brd4 and 7SK/HEXIM1 regulatory complexes.
  J Cell Physiol, 224, 84-93.  
20574533 G.Napolitano, S.Amente, V.Castiglia, B.Gargano, V.Ruda, X.Darzacq, O.Bensaude, B.Majello, and L.Lania (2010).
Caffeine prevents transcription inhibition and P-TEFb/7SK dissociation following UV-induced DNA damage.
  PLoS One, 5, e11245.  
20675720 I.Lebars, D.Martinez-Zapien, A.Durand, J.Coutant, B.Kieffer, and A.C.Dock-Bregeon (2010).
HEXIM1 targets a repeated GAUC motif in the riboregulator of transcription 7SK and promotes base pair rearrangements.
  Nucleic Acids Res, 38, 7749-7763.  
20053765 J.A.Frey, and V.Gandhi (2010).
8-Amino-adenosine inhibits multiple mechanisms of transcription.
  Mol Cancer Ther, 9, 236-245.  
20139419 M.R.López-Huertas, S.Callejas, D.Abia, E.Mateos, A.Dopazo, J.Alcamí, and M.Coiras (2010).
Modifications in host cell cytoskeleton structure and function mediated by intracellular HIV-1 Tat protein are greatly dependent on the second coding exon.
  Nucleic Acids Res, 38, 3287-3307.  
21035725 M.W.Nowicki, and M.D.Walkinshaw (2010).
CDK9 inhibitors push cancer cells over the edge.
  Chem Biol, 17, 1047-1048.  
20851342 S.Baumli, J.A.Endicott, and L.N.Johnson (2010).
Halogen bonds form the basis for selective P-TEFb inhibition by DRB.
  Chem Biol, 17, 931-936.
PDB codes: 3my1 3my5
21035734 S.Wang, G.Griffiths, C.A.Midgley, A.L.Barnett, M.Cooper, J.Grabarek, L.Ingram, W.Jackson, G.Kontopidis, S.J.McClue, C.McInnes, J.McLachlan, C.Meades, M.Mezna, I.Stuart, M.P.Thomas, D.I.Zheleva, D.P.Lane, R.C.Jackson, D.M.Glover, D.G.Blake, and P.M.Fischer (2010).
Discovery and characterization of 2-anilino-4- (thiazol-5-yl)pyrimidine transcriptional CDK inhibitors as anticancer agents.
  Chem Biol, 17, 1111-1121.
PDB codes: 2xmy 2xnb
20535204 T.H.Tahirov, N.D.Babayeva, K.Varzavand, J.J.Cooper, S.C.Sedore, and D.H.Price (2010).
Crystal structure of HIV-1 Tat complexed with human P-TEFb.
  Nature, 465, 747-751.
PDB codes: 3mi9 3mia
19603446 A.Ali, A.Ghosh, R.S.Nathans, N.Sharova, S.O'Brien, H.Cao, M.Stevenson, and T.M.Rana (2009).
Identification of flavopiridol analogues that selectively inhibit positive transcription elongation factor (P-TEFb) and block HIV-1 replication.
  Chembiochem, 10, 2072-2080.  
19297489 A.J.Kapasi, C.L.Clark, K.Tran, and D.H.Spector (2009).
Recruitment of cdk9 to the immediate-early viral transcriptosomes during human cytomegalovirus infection requires efficient binding to cyclin T1, a threshold level of IE2 86, and active transcription.
  J Virol, 83, 5904-5917.  
19542017 A.P.Rice (2009).
Dysregulation of positive transcription elongation factor B and myocardial hypertrophy.
  Circ Res, 104, 1327-1329.  
19828451 F.Vollmuth, W.Blankenfeldt, and M.Geyer (2009).
Structures of the dual bromodomains of the P-TEFb-activating protein Brd4 at atomic resolution.
  J Biol Chem, 284, 36547-36556.
PDB codes: 3jvj 3jvk 3jvl 3jvm
19136461 G.Lolli (2009).
Binding to DNA of the RNA-polymerase II C-terminal domain allows discrimination between Cdk7 and Cdk9 phosphorylation.
  Nucleic Acids Res, 37, 1260-1268.  
19223581 I.D'Orso, and A.D.Frankel (2009).
Tat acetylation modulates assembly of a viral-host RNA-protein transcription complex.
  Proc Natl Acad Sci U S A, 106, 3101-3106.  
19723344 J.Kohoutek (2009).
P-TEFb- the final frontier.
  Cell Div, 4, 19.  
19721463 J.Weigelt (2009).
The case for open-access chemical biology. A strategy for pre-competitive medicinal chemistry to promote drug discovery.
  EMBO Rep, 10, 941-945.  
19296866 L.N.Johnson (2009).
Protein kinase inhibitors: contributions from structure to clinical compounds.
  Q Rev Biophys, 42, 1.  
19237565 P.J.Day, A.Cleasby, I.J.Tickle, M.O'Reilly, J.E.Coyle, F.P.Holding, R.L.McMenamin, J.Yon, R.Chopra, C.Lengauer, and H.Jhoti (2009).
Crystal structure of human CDK4 in complex with a D-type cyclin.
  Proc Natl Acad Sci U S A, 106, 4166-4170.
PDB codes: 2w96 2w99 2w9f 2w9z
19741158 R.Ramakrishnan, E.C.Dow, and A.P.Rice (2009).
Characterization of Cdk9 T-loop phosphorylation in resting and activated CD4(+) T lymphocytes.
  J Leukoc Biol, 86, 1345-1350.  
19237555 T.Takaki, A.Echalier, N.R.Brown, T.Hunt, J.A.Endicott, and M.E.Noble (2009).
The structure of CDK4/cyclin D3 has implications for models of CDK activation.
  Proc Natl Acad Sci U S A, 106, 4171-4176.
PDB code: 3g33
19732026 W.Coley, K.Kehn-Hall, R.Van Duyne, and F.Kashanchi (2009).
Novel HIV-1 therapeutics through targeting altered host cell pathways.
  Expert Opin Biol Ther, 9, 1369-1382.  
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. Where a reference describes a PDB structure, the PDB codes are shown on the right.