PDBsum entry 3mia

Protein binding

PDB id: 3mia

Contents

Protein chains

325 a.a. *

247 a.a. *

48 a.a. *

Ligands

ANP

Metals

_MG

_ZN ×2

Waters ×27

* Residue conservation analysis

PDB id:

3mia

Name:

Protein binding

Title:

Crystal structure of HIV-1 tat complexed with atp-bound human p-tefb

Structure:

Cell division protein kinase 9. Chain: a. Fragment: unp residues 1-345, protein kinase domain. Synonym: cyclin-dependent kinase 9, serine/threonine-protein kinase 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.

Resolution:

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.H.Price

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

Date:

09-Apr-10 Release date: 09-Jun-10

Protein chain

P50750  (CDK9_HUMAN) -  Cyclin-dependent kinase 9 from Homo sapiens

Seq: 372 a.a.

Struc: 325 a.a.*

Protein chain

O60563  (CCNT1_HUMAN) -  Cyclin-T1 from Homo sapiens

Seq: 726 a.a.

Struc: 247 a.a.*

Protein chain

P04608  (TAT_HV1H2) -  Protein Tat from Human immunodeficiency virus type 1 group M subtype B (isolate HXB2)

Seq: 86 a.a.

Struc: 48 a.a.

* PDB and UniProt seqs differ at 2 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⁺

L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] (Bound ligand (Het Group name = ANP) matches with 81.25% similarity) + ADP + H(+)

L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] (Bound ligand (Het Group name = ANP) matches with 81.25% similarity) + 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⁺

[DNA-directed RNA polymerase] + ATP = phospho-[DNA-directed RNA polymerase] (Bound ligand (Het Group name = ANP) matches with 81.25% similarity) + 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

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.

ABSTRACT

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.