PDBsum entry 16pk

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Kinase PDB id
Protein chain
415 a.a. *
Waters ×580
* Residue conservation analysis
PDB id:
Name: Kinase
Title: Phosphoglycerate kinase from trypanosoma brucei bisubstrate analog
Structure: 3-phosphoglycerate kinase. Chain: a. Synonym: pgk. Engineered: yes. Mutation: yes
Source: Trypanosoma brucei. Organism_taxid: 5691. Variant: glycosomal version. Organelle: glycosome. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
1.60Å     R-factor:   0.188     R-free:   0.235
Authors: B.E.Bernstein,J.Bressi,M.Blackburn,M.Gelb,W.G.J.Hol
Key ref:
B.E.Bernstein et al. (1998). A bisubstrate analog induces unexpected conformational changes in phosphoglycerate kinase from Trypanosoma brucei. J Mol Biol, 279, 1137-1148. PubMed id: 9642090 DOI: 10.1006/jmbi.1998.1835
18-May-98     Release date:   25-Nov-98    
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Protein chain
Pfam   ArchSchema ?
P07378  (PGKC_TRYBB) -  Phosphoglycerate kinase, glycosomal
440 a.a.
415 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.  - Phosphoglycerate kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Calvin Cycle (carbon fixation stages)
      Reaction: ATP + 3-phospho-D-glycerate = ADP + 3-phospho-D-glyceroyl phosphate
+ 3-phospho-D-glycerate
Bound ligand (Het Group name = BIS)
matches with 65.00% similarity
+ 3-phospho-D-glyceroyl phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     glycosome   2 terms 
  Biological process     phosphorylation   2 terms 
  Biochemical function     nucleotide binding     5 terms  


DOI no: 10.1006/jmbi.1998.1835 J Mol Biol 279:1137-1148 (1998)
PubMed id: 9642090  
A bisubstrate analog induces unexpected conformational changes in phosphoglycerate kinase from Trypanosoma brucei.
B.E.Bernstein, D.M.Williams, J.C.Bressi, P.Kuhn, M.H.Gelb, G.M.Blackburn, W.G.Hol.
The glycolytic enzyme phosphoglycerate kinase (PGK) catalyzes phosphoryl transfer between 1,3-bis-phosphoglycerate and ADP to form 3-phosphoglycerate and ATP. During catalysis, a major hinge bending motion occurs which brings the N and C-terminal enzyme domains and their bound substrates together and in-line for phosphoryl transfer. We have crystallized Trypanosoma brucei PGK in the presence of the bisubstrate analog, adenylyl 1,1,5,5-tetrafluoropentane-1, 5-bisphosphonate, and solved the structure of this complex in two different crystal forms at 1.6 and 2.0 A resolution, obtained from PEG 8000 and ammonium phosphate solutions, respectively. These high resolution structures of PGK:inhibitor complexes are of particular interest for drug design since Trypanosoma brucei, the causative agent of African sleeping sickness, relies on glycolysis as its sole energy source. In both structures, the inhibitor is bound in a fully extended conformation with its adenosine moiety assuming exactly the same position as in ADP:PGK complexes and with its 5' phosphonate group occupying part of the 1,3-bis-phosphoglycerate binding site. The bisubstrate analog forces PGK to assume a novel, "inhibited" conformation, intermediate in hinge angle between the native structures of open and closed form PGK. These structures of enzyme-inhibitor complexes demonstrate that PGK has two distinct hinge points that can each be independently activated. In the "PEG" structure, the C-terminal hinge is partially activated while the N-terminal hinge point remains in an open state. In the "phosphate" structure, closure of the N-terminal hinge point is also evident. Finally and most unexpectedly, both complex structures also contain a 3 A shift of a helix that lies outside the flexible hinge region. We propose that a transient shift of this helix is a required element of PGK hinge closure during catalysis.
  Selected figure(s)  
Figure 2.
Figure 2. Schematic diagram of interactions between T. brucei PGK and inhibitor with all distances in angstroms. Protein residue identities are colored according to domain as in Figure 1 with N-terminal domain residues in blue, C-terminal domain residues in red, and hinge region residues in yellow. The inhibitor makes strong interactions with the C-terminal domain and the hinge region, as well as a quite limited, water-mediated, interaction with Gly 168 of the N-terminal domain.
Figure 5.
Figure 5. Close-up view of inhibitor binding and induced conformational change. Inhibitor is depicted as a stick figure, and protein as a ribbon with N-terminal domain, C-terminal domain, and hinge region in blue, red and yellow, respectively. In addition, the uninhibited state of helix 13, similar in the open and closed form PGK structures [Harlos et al 1992, Davies et al 1994 and Bernstein et al 1997], is depicted as a gray threaded ribbon. Helix 13 in the bisubstrate analog:PGK complex is translated by 3 Å with respect to its native state in open and closed form PGK.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1998, 279, 1137-1148) copyright 1998.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20065119 G.B.Gloor, G.Tyagi, D.M.Abrassart, A.J.Kingston, A.D.Fernandes, S.D.Dunn, and C.J.Brandl (2010).
Functionally compensating coevolving positions are neither homoplasic nor conserved in clades.
  Mol Biol Evol, 27, 1181-1191.  
21153779 N.Chandra, P.Anand, and K.Yeturu (2010).
Structural bioinformatics: Deriving biological insights from protein structures.
  Interdiscip Sci, 2, 347-366.  
19292872 R.Encalada, A.Rojo-Domínguez, J.S.Rodríguez-Zavala, J.P.Pardo, H.Quezada, R.Moreno-Sánchez, and E.Saavedra (2009).
Molecular basis of the unusual catalytic preference for GDP/GTP in Entamoeba histolytica 3-phosphoglycerate kinase.
  FEBS J, 276, 2037-2047.  
19058030 Y.Kim, H.Li, T.A.Binkowski, D.Holzle, and A.Joachimiak (2009).
Crystal structure of fatty acid/phospholipid synthesis protein PlsX from Enterococcus faecalis.
  J Struct Funct Genomics, 10, 157-163.
PDB code: 1u7n
18004764 G.M.Sawyer, A.F.Monzingo, E.C.Poteet, D.A.O'Brien, and J.D.Robertus (2008).
X-ray analysis of phosphoglycerate kinase 2, a sperm-specific isoform from Mus musculus.
  Proteins, 71, 1134-1144.
PDB codes: 2p9q 2p9t 2paa
15229886 N.Fernandez-Fuentes, A.Hermoso, J.Espadaler, E.Querol, F.X.Aviles, and B.Oliva (2004).
Classification of common functional loops of kinase super-families.
  Proteins, 56, 539-555.  
15345537 R.A.da Silva, L.Degrève, and A.Caliri (2004).
LMProt: an efficient algorithm for Monte Carlo sampling of protein conformational space.
  Biophys J, 87, 1567-1577.  
14997553 Z.Kovári, and M.Vas (2004).
Protein conformer selection by sequence-dependent packing contacts in crystals of 3-phosphoglycerate kinase.
  Proteins, 55, 198-209.  
12509431 D.L.Jakeman, A.J.Ivory, G.M.Blackburn, and M.P.Williamson (2003).
Orientation of 1,3-bisphosphoglycerate analogs bound to phosphoglycerate kinase.
  J Biol Chem, 278, 10957-10962.  
12023213 I.Z.Zubrzycki (2002).
Homology modeling and molecular dynamics study of NAD-dependent glycerol-3-phosphate dehydrogenase from Trypanosoma brucei rhodesiense, a potential target enzyme for anti-sleeping sickness drug development.
  Biophys J, 82, 2906-2915.  
12454459 P.Tougard, T.Bizebard, M.Ritco-Vonsovici, P.Minard, and M.Desmadril (2002).
Structure of a circularly permuted phosphoglycerate kinase.
  Acta Crystallogr D Biol Crystallogr, 58, 2018-2023.
PDB code: 1fw8
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.