PDBsum entry 1vpe

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protein ligands metals links
Transferase PDB id
Protein chain
398 a.a. *
Waters ×226
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystallographic analysis of phosphoglycerate kinase from the hyperthermophilic bacterium thermotoga maritima
Structure: Phosphoglycerate kinase. Chain: a. Engineered: yes
Source: Thermotoga maritima. Organism_taxid: 2336. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.00Å     R-factor:   0.198     R-free:   0.288
Authors: G.Auerbach,R.Huber,M.Graettinger,K.Zaiss,H.Schurig, R.Jaenicke,U.Jacob
Key ref:
G.Auerbach et al. (1997). Closed structure of phosphoglycerate kinase from Thermotoga maritima reveals the catalytic mechanism and determinants of thermal stability. Structure, 5, 1475-1483. PubMed id: 9384563 DOI: 10.1016/S0969-2126(97)00297-9
06-May-97     Release date:   17-Jun-98    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P36204  (PGKT_THEMA) -  Bifunctional PGK/TIM
654 a.a.
398 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 5 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class 2: 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
Bound ligand (Het Group name = 3PG)
corresponds exactly
Bound ligand (Het Group name = ANP)
matches with 81.00% similarity
+ 3-phospho-D-glyceroyl phosphate
   Enzyme class 3: E.C.  - Triose-phosphate isomerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: D-glyceraldehyde 3-phosphate = glycerone phosphate
D-glyceraldehyde 3-phosphate
Bound ligand (Het Group name = 3PG)
matches with 90.00% similarity
= glycerone 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     glycolysis   1 term 
  Biochemical function     phosphoglycerate kinase activity     1 term  


DOI no: 10.1016/S0969-2126(97)00297-9 Structure 5:1475-1483 (1997)
PubMed id: 9384563  
Closed structure of phosphoglycerate kinase from Thermotoga maritima reveals the catalytic mechanism and determinants of thermal stability.
G.Auerbach, R.Huber, M.Grättinger, K.Zaiss, H.Schurig, R.Jaenicke, U.Jacob.
BACKGROUND: Phosphoglycerate kinase (PGK) is essential in most living cells both for ATP generation in the glycolytic pathway of aerobes and for fermentation in anaerobes. In addition, in many plants the enzyme is involved in carbon fixation. Like other kinases, PGK folds into two distinct domains, which undergo a large hinge-bending motion upon catalysis. The monomeric 45 kDa enzyme catalyzes the transfer of the C1-phosphoryl group from 1, 3-bisphosphoglycerate to ADP to form 1,3-bisphosphoglycerate to ADP to form 3-phosphoglycerate and ATP. For decades, the conformation of the enzyme during catalysis has been enigmatic. The crystal structure of PGK from the hyperthermophilic organism Thermotoga maritima (TmPGK) represents the first structure of an extremely thermostable PGK. It adds to a series of four known crystal structures of PGKs from mesophilic via moderately thermophilic to a hyperthermophilic organism, allowing a detailed analysis of possible structural determinants of thermostability. RESULTS: The crystal structure of TmPGK was determined to 2.0 A resolution, as a ternary complex with the product 3-phosphoglycerate and the product analogue AMP-PNP (adenylyl-imido diphosphate). The complex crystallizes in a closed conformation with a drastically reduced inter-domain angle and a distance between the two bound ligands of 4.4 A, presumably representing the active conformation of the enzyme. The structure provides new details of the catalytic mechanism. An inter-domain salt bridge between residues Arg62 and Asp200 forms a strap to hold the two domains in the closed state. We identify Lys197 as a residue involved in stabilization of the transition state phosphoryl group, and so term it the 'phosphoryl gripper'. CONCLUSIONS: The hinge-bending motion of the two domains upon closure of the structure, as seen in the Trypanosoma PGK structure, is confirmed. This closed conformation obviously occurs after binding of both substrates and is locked by the Arg62-Asp200 salt bridge. Re-orientations in the conserved active-site loop region around Thr374 also bring both domains into direct contact in the core region of the former inter-domain cleft, to form the complete catalytic site. Comparison of extremely thermostable TmPGK with less thermostable homologues reveals that its increased rigidity is achieved by a raised number of intramolecular interactions, such as an increased number of ion pairs and additional stabilization of alpha helix and loop regions. The covalent fusion with triosephosphate isomerase might represent an additional stabilization strategy.
  Selected figure(s)  
Figure 3.
Figure 3. Stereo view of the superposition of the closed structure of TmPGK (black) with the open structure of BsPGK (red). The central water of the TmPGK structure is shown in blue. A large motion of residue Thr374 (Thr371; BsPGK) towards Arg36 causes a subsequent reorientation of the C-terminal residues Gly375-Gly377 (not labelled). The closed conformation is locked by an inter-domain salt bridge between Arg62 and Asp200 (green). The difference between the inter-domain angles in TmPGK and BsPGK, a[TM] and a[BS], respectively, is 21.
  The above figure is reprinted by permission from Cell Press: Structure (1997, 5, 1475-1483) copyright 1997.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
19422062 Z.Palmai, L.Chaloin, C.Lionne, J.Fidy, D.Perahia, and E.Balog (2009).
Substrate binding modifies the hinge bending characteristics of human 3-phosphoglycerate kinase: a molecular dynamics study.
  Proteins, 77, 319-329.  
18463139 C.Gondeau, L.Chaloin, P.Lallemand, B.Roy, C.Périgaud, T.Barman, A.Varga, M.Vas, C.Lionne, and S.T.Arold (2008).
Molecular basis for the lack of enantioselectivity of human 3-phosphoglycerate kinase.
  Nucleic Acids Res, 36, 3620-3629.
PDB codes: 2zgv 3c39 3c3a 3c3b 3c3c
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
17158564 E.Balog, M.Laberge, and J.Fidy (2007).
The influence of interdomain interactions on the intradomain motions in yeast phosphoglycerate kinase: a molecular dynamics study.
  Biophys J, 92, 1709-1716.  
17459874 L.Miallau, W.N.Hunter, S.M.McSweeney, and G.A.Leonard (2007).
Structures of Staphylococcus aureus D-tagatose-6-phosphate kinase implicate domain motions in specificity and mechanism.
  J Biol Chem, 282, 19948-19957.
PDB codes: 2jg1 2jgv
17455908 Y.O.You, and W.A.van der Donk (2007).
Mechanistic investigations of the dehydration reaction of lacticin 481 synthetase using site-directed mutagenesis.
  Biochemistry, 46, 5991-6000.  
15819882 A.Varga, B.Flachner, E.Gráczer, S.Osváth, A.N.Szilágyi, and M.Vas (2005).
Correlation between conformational stability of the ternary enzyme-substrate complex and domain closure of 3-phosphoglycerate kinase.
  FEBS J, 272, 1867-1885.  
15774882 C.Ingram-Smith, A.Gorrell, S.H.Lawrence, P.Iyer, K.Smith, and J.G.Ferry (2005).
Characterization of the acetate binding pocket in the Methanosarcina thermophila acetate kinase.
  J Bacteriol, 187, 2386-2394.  
15251041 C.Strub, C.Alies, A.Lougarre, C.Ladurantie, J.Czaplicki, and D.Fournier (2004).
Mutation of exposed hydrophobic amino acids to arginine to increase protein stability.
  BMC Biochem, 5, 9.  
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.  
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.  
14611665 P.Jordan, L.A.Snyder, and N.J.Saunders (2003).
Diversity in coding tandem repeats in related Neisseria spp.
  BMC Microbiol, 3, 23.  
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
12005432 S.Ramón-Maiques, A.Marina, F.Gil-Ortiz, I.Fita, and V.Rubio (2002).
Structure of acetylglutamate kinase, a key enzyme for arginine biosynthesis and a prototype for the amino acid kinase enzyme family, during catalysis.
  Structure, 10, 329-342.
PDB codes: 1gs5 1gsj
11248706 A.N.Szilágyi, N.V.Kotova, G.V.Semisotnov, and M.Vas (2001).
Incomplete refolding of a fragment of the N-terminal domain of pig muscle 3-phosphoglycerate kinase that lacks a subdomain. Comparison with refolding of the complementary C-terminal fragment.
  Eur J Biochem, 268, 1851-1860.  
11238984 C.Vieille, and G.J.Zeikus (2001).
Hyperthermophilic enzymes: sources, uses, and molecular mechanisms for thermostability.
  Microbiol Mol Biol Rev, 65, 1.  
11679738 D.Mandelman, M.Bentahir, G.Feller, C.Gerday, and R.Haser (2001).
Crystallization and preliminary X-ray analysis of a bacterial psychrophilic enzyme, phosphoglycerate kinase.
  Acta Crystallogr D Biol Crystallogr, 57, 1666-1668.  
10801491 A.Szilágyi, and P.Závodszky (2000).
Structural differences between mesophilic, moderately thermophilic and extremely thermophilic protein subunits: results of a comprehensive survey.
  Structure, 8, 493-504.  
11114510 H.Erlandsen, E.E.Abola, and R.C.Stevens (2000).
Combining structural genomics and enzymology: completing the picture in metabolic pathways and enzyme active sites.
  Curr Opin Struct Biol, 10, 719-730.  
10753921 M.Bentahir, G.Feller, M.Aittaleb, J.Lamotte-Brasseur, T.Himri, J.P.Chessa, and C.Gerday (2000).
Structural, kinetic, and calorimetric characterization of the cold-active phosphoglycerate kinase from the antarctic Pseudomonas sp. TACII18.
  J Biol Chem, 275, 11147-11153.  
10782993 M.C.Wahl, R.Huber, S.Marinkoviç, E.Weyher-Stingl, and S.Ehlert (2000).
Structural investigations of the highly flexible recombinant ribosomal protein L12 from Thermotoga maritima.
  Biol Chem, 381, 221-229.  
10194385 K.Zaiss, and R.Jaenicke (1999).
Thermodynamic study of phosphoglycerate kinase from Thermotoga maritima and its isolated domains: reversible thermal unfolding monitored by differential scanning calorimetry and circular dichroism spectroscopy.
  Biochemistry, 38, 4633-4639.  
  10593256 S.Kumar, B.Ma, C.J.Tsai, H.Wolfson, and R.Nussinov (1999).
Folding funnels and conformational transitions via hinge-bending motions.
  Cell Biochem Biophys, 31, 141-164.  
10545331 W.Grabarse, M.Vaupel, J.A.Vorholt, S.Shima, R.K.Thauer, A.Wittershagen, G.Bourenkov, H.D.Bartunik, and U.Ermler (1999).
The crystal structure of methenyltetrahydromethanopterin cyclohydrolase from the hyperthermophilic archaeon Methanopyrus kandleri.
  Structure, 7, 1257-1268.
PDB code: 1qlm
9562560 A.Matte, L.W.Tari, and L.T.Delbaere (1998).
How do kinases transfer phosphoryl groups?
  Structure, 6, 413-419.  
9622507 A.N.Szilágyi, and M.Vas (1998).
Anion activation of 3-phosphoglycerate kinase requires domain closure.
  Biochemistry, 37, 8551-8563.  
9521762 B.E.Bernstein, and W.G.Hol (1998).
Crystal structures of substrates and products bound to the phosphoglycerate kinase active site reveal the catalytic mechanism.
  Biochemistry, 37, 4429-4436.  
9753433 K.Gruber, G.Klintschar, M.Hayn, A.Schlacher, W.Steiner, and C.Kratky (1998).
Thermophilic xylanase from Thermomyces lanuginosus: high-resolution X-ray structure and modeling studies.
  Biochemistry, 37, 13475-13485.
PDB code: 1yna
9860830 M.W.Bauer, and R.M.Kelly (1998).
The family 1 beta-glucosidases from Pyrococcus furiosus and Agrobacterium faecalis share a common catalytic mechanism.
  Biochemistry, 37, 17170-17178.  
9914256 R.Jaenicke, and G.Böhm (1998).
The stability of proteins in extreme environments.
  Curr Opin Struct Biol, 8, 738-748.  
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.