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PDBsum entry 3f61
Go to PDB code: 
protein ligands metals links
Transferase PDB id
3f61

 

 

 

 

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Contents
Protein chain
271 a.a. *
Ligands
ADP
Metals
_MG ×4
Waters ×184
* Residue conservation analysis
PDB id:
3f61
Name: Transferase
Title: Crystal structure of m. Tuberculosis pknb leu33asp/val222asp double mutant in complex with adp
Structure: Serine/threonine-protein kinase pknb. Chain: a. Fragment: pknb kinase domain. Engineered: yes. Mutation: yes
Source: Mycobacterium tuberculosis. Organism_taxid: 1773. Strain: h37rv. Gene: mt0017, mtcy10h4.14c, pknb, rv0014c. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.80Å     R-factor:   0.205     R-free:   0.228
Authors: C.A.Mieczkowski,T.Alber,Tb Structural Genomics Consortium (Tbsgc)
Key ref: C.Mieczkowski et al. (2008). Auto-activation mechanism of the Mycobacterium tuberculosis PknB receptor Ser/Thr kinase. Embo J, 27, 3186-3197. PubMed id: 19008858
Date:
05-Nov-08     Release date:   02-Dec-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P9WI81  (PKNB_MYCTU) -  Serine/threonine-protein kinase PknB from Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Seq:
Struc: 		 
Seq:
Struc: 		626 a.a.
271 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.2.7.11.1  - non-specific serine/threonine protein 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]
Bound ligand (Het Group name = ADP)
corresponds exactly 		+ ADP
 + H(+)
L-threonyl-[protein]
 + ATP
 = O-phospho-L-threonyl-[protein]
Bound ligand (Het Group name = ADP)
corresponds exactly 		+ ADP
 + H(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
Embo J 27:3186-3197 (2008)
PubMed id: 19008858  
 
 
Auto-activation mechanism of the Mycobacterium tuberculosis PknB receptor Ser/Thr kinase.
C.Mieczkowski, A.T.Iavarone, T.Alber.
 
  ABSTRACT  
 
Many Ser/Thr protein kinases are activated by autophosphorylation, but the mechanism of this process has not been defined. We determined the crystal structure of a mutant of the Ser/Thr kinase domain (KD) of the mycobacterial sensor kinase PknB in complex with an ATP competitive inhibitor and discovered features consistent with an activation complex. The complex formed an asymmetric dimer, with the G helix and the ordered activation loop of one KD in contact with the G helix of the other. The activation loop of this putative 'substrate' KD was disordered, with the ends positioned at the entrance to the partner KD active site. Single amino-acid substitutions in the G-helix interface reduced activation-loop phosphorylation, and multiple replacements abolished KD phosphorylation and kinase activation. Phosphorylation of an inactive mutant KD was reduced by G-helix substitutions in both active and inactive KDs, as predicted by the idea that the asymmetric dimer mimics a trans-autophosphorylation complex. These results support a model in which a structurally and functionally asymmetric, 'front-to-front' association mediates autophosphorylation of PknB and homologous kinases.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21208192 A.Ruggiero, F.Squeglia, D.Marasco, R.Marchetti, A.Molinaro, and R.Berisio (2011).
X-ray structural studies of the entire extracellular region of the serine/threonine kinase PrkC from Staphylococcus aureus.
  Biochem J, 435, 33-41.
PDB code: 3py9
21342471 G.Jones, R.Del Sol, E.Dudley, and P.Dyson (2011).
Forkhead-associated proteins genetically linked to the serine/threonine kinase PknB regulate carbon flux towards antibiotic biosynthesis in Streptomyces coelicolor.
  Microb Biotechnol, 4, 263-274.  
20520732 G.Arora, A.Sajid, M.Gupta, A.Bhaduri, P.Kumar, S.Basu-Modak, and Y.Singh (2010).
Understanding the role of PknJ in Mycobacterium tuberculosis: biochemical characterization and identification of novel substrate pyruvate kinase A.
  PLoS One, 5, e10772.  
20185505 J.Jang, A.Stella, F.Boudou, F.Levillain, E.Darthuy, J.Vaubourgeix, C.Wang, F.Bardou, G.Puzo, M.Gilleron, O.Burlet-Schiltz, B.Monsarrat, P.Brodin, B.Gicquel, and O.Neyrolles (2010).
Functional characterization of the Mycobacterium tuberculosis serine/threonine kinase PknJ.
  Microbiology, 156, 1619-1631.  
20336234 O.A.Gani, and R.A.Engh (2010).
Protein kinase inhibition of clinically important staurosporine analogues.
  Nat Prod Rep, 27, 489-498.  
20462494 P.Barthe, G.V.Mukamolova, C.Roumestand, and M.Cohen-Gonsaud (2010).
The structure of PknB extracellular PASTA domain from mycobacterium tuberculosis suggests a ligand-dependent kinase activation.
  Structure, 18, 606-615.
PDB codes: 2kud 2kue 2kuf 2kui
21134645 T.N.Lombana, N.Echols, M.C.Good, N.D.Thomsen, H.L.Ng, A.E.Greenstein, A.M.Falick, D.S.King, and T.Alber (2010).
Allosteric activation mechanism of the Mycobacterium tuberculosis receptor Ser/Thr protein kinase, PknB.
  Structure, 18, 1667-1677.  
19638631 D.Tiwari, R.K.Singh, K.Goswami, S.K.Verma, B.Prakash, and V.K.Nandicoori (2009).
Key residues in Mycobacterium tuberculosis protein kinase G play a role in regulating kinase activity and survival in the host.
  J Biol Chem, 284, 27467-27479.  
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 code is shown on the right.

 

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