PDBsum entry 3mia

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protein ligands metals Protein-protein interface(s) links
Protein binding PDB id
Protein chains
325 a.a. *
247 a.a. *
48 a.a. *
_ZN ×2
Waters ×27
* Residue conservation analysis
PDB id:
Name: Protein binding
Title: Crystal structure of HIV-1 tat complexed with atp-bound huma
Structure: Cell division protein kinase 9. Chain: a. Fragment: unp residues 1-345, protein kinase domain. Synonym: cyclin-dependent kinase 9, serine/threonine-protei pitalre, cell division cycle 2-like protein kinase 4, c-2k. Engineered: yes. Cyclin-t1. Chain: b. Fragment: unp residues 1-266.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: cdc2l4, cdk9. Expressed in: spodoptera frugiperda. Expression_system_cell: insect cells. K2420). Gene: ccnt1, cyclin t1. Human immunodeficiency virus type 1.
3.00Å     R-factor:   0.219     R-free:   0.287
Authors: T.H.Tahirov,N.D.Babayeva,K.Varzavand,J.J.Cooper,S.C.Sedore,D
Key ref: T.H.Tahirov et al. (2010). Crystal structure of HIV-1 Tat complexed with human P-TEFb. Nature, 465, 747-751. PubMed id: 20535204
09-Apr-10     Release date:   09-Jun-10    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P50750  (CDK9_HUMAN) -  Cyclin-dependent kinase 9
372 a.a.
325 a.a.*
Protein chain
Pfam   ArchSchema ?
O60563  (CCNT1_HUMAN) -  Cyclin-T1
726 a.a.
247 a.a.*
Protein chain
Pfam   ArchSchema ?
P04608  (TAT_HV1H2) -  Protein Tat
86 a.a.
48 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 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
+ protein
Bound ligand (Het Group name = ANP)
matches with 81.00% similarity
+ 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
+ [DNA-directed RNA polymerase]
Bound ligand (Het Group name = ANP)
matches with 81.00% similarity
+ [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!
  Cellular component     extracellular region   13 terms 
  Biological process     viral reproduction   27 terms 
  Biochemical function     transcription regulatory region DNA binding     19 terms  


Nature 465:747-751 (2010)
PubMed id: 20535204  
Crystal structure of HIV-1 Tat complexed with human P-TEFb.
T.H.Tahirov, N.D.Babayeva, K.Varzavand, J.J.Cooper, S.C.Sedore, D.H.Price.
Regulation of the expression of the human immunodeficiency virus (HIV) genome is accomplished in large part by controlling transcription elongation. The viral protein Tat hijacks the host cell's RNA polymerase II elongation control machinery through interaction with the positive transcription elongation factor, P-TEFb, and directs the factor to promote productive elongation of HIV mRNA. Here we describe the crystal structure of the Tat.P-TEFb complex containing HIV-1 Tat, human Cdk9 (also known as CDK9), and human cyclin T1 (also known as CCNT1). Tat adopts a structure complementary to the surface of P-TEFb and makes extensive contacts, mainly with the cyclin T1 subunit of P-TEFb, but also with the T-loop of the Cdk9 subunit. The structure provides a plausible explanation for the tolerance of Tat to sequence variations at certain sites. Importantly, Tat induces significant conformational changes in P-TEFb. This finding lays a foundation for the design of compounds that would specifically inhibit the Tat.P-TEFb complex and block HIV replication.

Literature references that cite this PDB file's key reference

  PubMed id Reference
22421880 A.Engelman, and P.Cherepanov (2012).
The structural biology of HIV-1: mechanistic and therapeutic insights.
  Nat Rev Microbiol, 10, 279-290.  
21135120 J.Guo, M.Garrett, G.Micklem, and S.Brogna (2011).
Poly(A) signals located near the 5' end of genes are silenced by a general mechanism that prevents premature 3'-end processing.
  Mol Cell Biol, 31, 639-651.  
21204735 M.K.Johri, R.Mishra, C.Chhatbar, S.K.Unni, and S.K.Singh (2011).
Tits and bits of HIV Tat protein.
  Expert Opin Biol Ther, 11, 269-283.  
20808803 B.J.Krueger, K.Varzavand, J.J.Cooper, and D.H.Price (2010).
The mechanism of release of P-TEFb and HEXIM1 from the 7SK snRNP by viral and cellular activators includes a conformational change in 7SK.
  PLoS One, 5, e12335.  
  20942971 F.L.Tansi, V.Blanchard, M.Berger, R.Tauber, W.Reutter, and H.Fan (2010).
Interaction of human dipeptidyl peptidase IV and human immunodeficiency virus type-1 transcription transactivator in Sf9 cells.
  Virol J, 7, 267.  
20683478 M.Barboric, and T.Lenasi (2010).
Kick-sTARting HIV-1 transcription elongation by 7SK snRNP deporTATion.
  Nat Struct Mol Biol, 17, 928-930.  
21035725 M.W.Nowicki, and M.D.Walkinshaw (2010).
CDK9 inhibitors push cancer cells over the edge.
  Chem Biol, 17, 1047-1048.  
20721684 R.Pierleoni, M.Menotta, A.Antonelli, C.Sfara, G.Serafini, S.Dominici, M.E.Laguardia, A.Salis, G.Damonte, L.Banci, M.Porcu, P.Monini, B.Ensoli, and M.Magnani (2010).
Effect of the redox state on HIV-1 tat protein multimerization and cell internalization and trafficking.
  Mol Cell Biochem, 345, 105-118.  
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.