PDBsum entry 1fwk

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protein ligands metals Protein-protein interface(s) links
Transferase PDB id
Protein chains
296 a.a. *
ADP ×4
Waters ×596
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystal structure of homoserine kinase complexed with adp
Structure: Homoserine kinase. Chain: a, b, c, d. Synonym: hk. Engineered: yes
Source: Methanocaldococcus jannaschii. Organism_taxid: 2190. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Tetramer (from PQS)
2.10Å     R-factor:   0.209     R-free:   0.246
Authors: T.Zhou,M.Daugherty,N.V.Grishin,A.L.Osterman,H.Zhang
Key ref:
T.Zhou et al. (2000). Structure and mechanism of homoserine kinase: prototype for the GHMP kinase superfamily. Structure, 8, 1247-1257. PubMed id: 11188689 DOI: 10.1016/S0969-2126(00)00533-5
22-Sep-00     Release date:   20-Dec-00    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q58504  (KHSE_METJA) -  Homoserine kinase
296 a.a.
296 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Homoserine kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Threonine Biosynthesis
      Reaction: ATP + L-homoserine = ADP + O-phospho-L-homoserine
+ L-homoserine
Bound ligand (Het Group name = ADP)
corresponds exactly
+ O-phospho-L-homoserine
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     phosphorylation   4 terms 
  Biochemical function     nucleotide binding     5 terms  


DOI no: 10.1016/S0969-2126(00)00533-5 Structure 8:1247-1257 (2000)
PubMed id: 11188689  
Structure and mechanism of homoserine kinase: prototype for the GHMP kinase superfamily.
T.Zhou, M.Daugherty, N.V.Grishin, A.L.Osterman, H.Zhang.
BACKGROUND: Homoserine kinase (HSK) catalyzes an important step in the threonine biosynthesis pathway. It belongs to a large yet unique class of small metabolite kinases, the GHMP kinase superfamily. Members in the GHMP superfamily participate in several essential metabolic pathways, such as amino acid biosynthesis, galactose metabolism, and the mevalonate pathway. RESULTS: The crystal structure of HSK and its complex with ADP reveal a novel nucleotide binding fold. The N-terminal domain contains an unusual left-handed betaalphabeta unit, while the C-terminal domain has a central alpha-beta plait fold with an insertion of four helices. The phosphate binding loop in HSK is distinct from the classical P loops found in many ATP/GTP binding proteins. The bound ADP molecule adopts a rare syn conformation and is in the opposite orientation from those bound to the P loop-containing proteins. Inspection of the substrate binding cavity indicates several amino acid residues that are likely to be involved in substrate binding and catalysis. CONCLUSIONS: The crystal structure of HSK is the first representative in the GHMP superfamily to have determined structure. It provides insight into the structure and nucleotide binding mechanism of not only the HSK family but also a variety of enzymes in the GHMP superfamily. Such enzymes include galactokinases, mevalonate kinases, phosphomevalonate kinases, mevalonate pyrophosphate decarboxylases, and several proteins of yet unknown functions.
  Selected figure(s)  
Figure 5.
Figure 5. Ribbon Presentation of HSK DimerThe N- and C-terminal domains in monomer 1 (left) are colored green and cyan, respectively; they are colored yellow and orange, respectively, in monomer 2 (right). The bound ADP molecules are shown in a ball-and-stick representation

  The above figure is reprinted by permission from Cell Press: Structure (2000, 8, 1247-1257) copyright 2000.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19509296 C.Fan, H.J.Fromm, and T.A.Bobik (2009).
Kinetic and functional analysis of L-threonine kinase, the PduX enzyme of Salmonella enterica.
  J Biol Chem, 284, 20240-20248.  
18793870 H.Eoh, P.J.Brennan, and D.C.Crick (2009).
The Mycobacterium tuberculosis MEP (2C-methyl-d-erythritol 4-phosphate) pathway as a new drug target.
  Tuberculosis (Edinb), 89, 1.  
20064433 H.Eoh, P.Narayanasamy, A.C.Brown, T.Parish, P.J.Brennan, and D.C.Crick (2009).
Expression and characterization of soluble 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase from bacterial pathogens.
  Chem Biol, 16, 1230-1239.  
19191736 J.B.Thoden, P.D.Cook, C.Schäffer, P.Messner, and H.M.Holden (2009).
Structural and functional studies of QdtC: an N-acetyltransferase required for the biosynthesis of dTDP-3-acetamido-3,6-dideoxy-alpha-D-glucose.
  Biochemistry, 48, 2699-2709.
PDB codes: 3fs8 3fsb 3fsc
18848949 J.Carrero-Lérida, G.Pérez-Moreno, V.M.Castillo-Acosta, L.M.Ruiz-Pérez, and D.González-Pacanowska (2009).
Intracellular location of the early steps of the isoprenoid biosynthetic pathway in the trypanosomatids Leishmania major and Trypanosoma brucei.
  Int J Parasitol, 39, 307-314.  
19485344 J.L.Andreassi, M.W.Vetting, P.W.Bilder, S.L.Roderick, and T.S.Leyh (2009).
Structure of the ternary complex of phosphomevalonate kinase: the enzyme and its family.
  Biochemistry, 48, 6461-6468.
PDB code: 3gon
19542002 M.S.Saldías, and M.A.Valvano (2009).
Interactions of Burkholderia cenocepacia and other Burkholderia cepacia complex bacteria with epithelial and phagocytic cells.
  Microbiology, 155, 2809-2817.  
18494797 A.K.Nair, M.A.Young, and K.M.Menon (2008).
Regulation of luteinizing hormone receptor mRNA expression by mevalonate kinase--role of the catalytic center in mRNA recognition.
  FEBS J, 275, 3397-3407.  
18245852 C.Q.Diep, X.Tao, V.Pilauri, M.Losiewicz, T.E.Blank, and J.E.Hopper (2008).
Genetic evidence for sites of interaction between the Gal3 and Gal80 proteins of the Saccharomyces cerevisiae GAL gene switch.
  Genetics, 178, 725-736.  
18490662 K.J.Wierenga, K.Lai, P.Buchwald, and M.Tang (2008).
High-throughput screening for human galactokinase inhibitors.
  J Biomol Screen, 13, 415-423.  
18823933 N.E.Voynova, Z.Fu, K.P.Battaile, T.J.Herdendorf, J.J.Kim, and H.M.Miziorko (2008).
Human mevalonate diphosphate decarboxylase: characterization, investigation of the mevalonate diphosphate binding site, and crystal structure.
  Arch Biochem Biophys, 480, 58-67.
PDB code: 3d4j
18422643 T.Sgraja, M.S.Alphey, S.Ghilagaber, R.Marquez, M.N.Robertson, J.L.Hemmings, S.Lauw, F.Rohdich, A.Bacher, W.Eisenreich, V.Illarionova, and W.N.Hunter (2008).
Characterization of Aquifex aeolicus 4-diphosphocytidyl-2C-methyl-d-erythritol kinase - ligand recognition in a template for antimicrobial drug discovery.
  FEBS J, 275, 2779-2794.
PDB codes: 2v2z 2v34 2v8p
17154432 A.K.Hirsch, F.R.Fischer, and F.Diederich (2007).
Phosphate recognition in structural biology.
  Angew Chem Int Ed Engl, 46, 338-352.  
17400916 J.L.Andreassi, P.W.Bilder, M.W.Vetting, S.L.Roderick, and T.S.Leyh (2007).
Crystal structure of the Streptococcus pneumoniae mevalonate kinase in complex with diphosphomevalonate.
  Protein Sci, 16, 983-989.
PDB code: 2oi2
17055149 K.M.Menon, A.K.Nair, L.Wang, and H.Peegel (2007).
Regulation of luteinizing hormone receptor mRNA expression by a specific RNA binding protein in the ovary.
  Mol Cell Endocrinol, 260, 109-116.  
17341835 T.Kotake, S.Hojo, D.Yamaguchi, T.Aohara, T.Konishi, and Y.Tsumuraya (2007).
Properties and physiological functions of UDP-sugar pyrophosphorylase in Arabidopsis.
  Biosci Biotechnol Biochem, 71, 761-771.  
17397541 T.Sgraja, T.K.Smith, and W.N.Hunter (2007).
Structure, substrate recognition and reactivity of Leishmania major mevalonate kinase.
  BMC Struct Biol, 7, 20.
PDB codes: 2hfs 2hfu
16219783 C.Q.Diep, G.Peng, M.Bewley, V.Pilauri, I.Ropson, and J.E.Hopper (2006).
Intragenic suppression of Gal3C interaction with Gal80 in the Saccharomyces cerevisiae GAL gene switch.
  Genetics, 172, 77-87.  
16525757 R.A.Azevedo, M.Lancien, and P.J.Lea (2006).
The aspartic acid metabolic pathway, an exciting and essential pathway in plants.
  Amino Acids, 30, 143-162.  
16263716 A.K.Nair, and K.M.Menon (2005).
Regulation of luteinizing hormone receptor expression: evidence of translational suppression in vitro by a hormonally regulated mRNA-binding protein and its endogenous association with luteinizing hormone receptor mRNA in the ovary.
  J Biol Chem, 280, 42809-42816.  
16160853 A.Lakshminarasimhan, and P.J.Bhat (2005).
Replacement of a conserved tyrosine by tryptophan in Gal3p of Saccharomyces cerevisiae reduces constitutive activity: implications for signal transduction in the GAL regulon.
  Mol Genet Genomics, 274, 384-393.  
15590630 J.B.Thoden, D.J.Timson, R.J.Reece, and H.M.Holden (2005).
Molecular structure of human galactokinase: implications for type II galactosemia.
  J Biol Chem, 280, 9662-9670.
PDB code: 1wuu
16006554 J.B.Thoden, and H.M.Holden (2005).
The molecular architecture of human N-acetylgalactosamine kinase.
  J Biol Chem, 280, 32784-32791.
PDB codes: 2a2c 2a2d
15802646 S.S.Doun, J.W.Burgner, S.D.Briggs, and V.W.Rodwell (2005).
Enterococcus faecalis phosphomevalonate kinase.
  Protein Sci, 14, 1134-1139.  
14749336 A.K.Nair, and K.M.Menon (2004).
Isolation and characterization of a novel trans-factor for luteinizing hormone receptor mRNA from ovary.
  J Biol Chem, 279, 14937-14944.  
14763977 B.Seiboth, L.Hartl, M.Pail, E.Fekete, L.Karaffa, and C.P.Kubicek (2004).
The galactokinase of Hypocrea jecorina is essential for cellulase induction by lactose but dispensable for growth on d-galactose.
  Mol Microbiol, 51, 1015-1025.  
14668203 K.M.Menon, U.M.Munshi, C.L.Clouser, and A.K.Nair (2004).
Regulation of luteinizing hormone/human chorionic gonadotropin receptor expression: a perspective.
  Biol Reprod, 70, 861-866.  
14767074 M.Hedl, and V.W.Rodwell (2004).
Enterococcus faecalis mevalonate kinase.
  Protein Sci, 13, 687-693.  
14724278 S.C.Sinha, B.N.Chaudhuri, J.W.Burgner, G.Yakovleva, V.J.Davisson, and J.L.Smith (2004).
Crystal structure of imidazole glycerol-phosphate dehydratase: duplication of an unusual fold.
  J Biol Chem, 279, 15491-15498.
PDB code: 1rhy
14699121 S.K.Singh, K.Yang, S.Karthikeyan, T.Huynh, X.Zhang, M.A.Phillips, and H.Zhang (2004).
The thrH gene product of Pseudomonas aeruginosa is a dual activity enzyme with a novel phosphoserine:homoserine phosphotransferase activity.
  J Biol Chem, 279, 13166-13173.
PDB codes: 1rku 1rkv
12694189 D.J.Timson, and R.J.Reece (2003).
Functional analysis of disease-causing mutations in human galactokinase.
  Eur J Biochem, 270, 1767-1774.  
12424232 D.Pilloff, K.Dabovic, M.J.Romanowski, J.B.Bonanno, M.Doherty, S.K.Burley, and T.S.Leyh (2003).
The kinetic mechanism of phosphomevalonate kinase.
  J Biol Chem, 278, 4510-4515.  
14501125 Geus, A.P.Hartley, S.E.Sedelnikova, S.E.Glynn, P.J.Baker, C.H.Verhees, J.van der Oost, and D.W.Rice (2003).
Cloning, purification, crystallization and preliminary crystallographic analysis of galactokinase from Pyrococcus furiosus.
  Acta Crystallogr D Biol Crystallogr, 59, 1819-1821.  
12923184 H.M.Holden, I.Rayment, and J.B.Thoden (2003).
Structure and function of enzymes of the Leloir pathway for galactose metabolism.
  J Biol Chem, 278, 43885-43888.  
12796487 J.B.Thoden, and H.M.Holden (2003).
Molecular structure of galactokinase.
  J Biol Chem, 278, 33305-33311.
PDB code: 1pie
12672694 J.G.Luz, C.A.Hassig, C.Pickle, A.Godzik, B.J.Meyer, and I.A.Wilson (2003).
XOL-1, primary determinant of sexual fate in C. elegans, is a GHMP kinase family member and a structural prototype for a class of developmental regulators.
  Genes Dev, 17, 977-990.
PDB code: 1mg7
12746447 R.Ishii, O.Nureki, and S.Yokoyama (2003).
Crystal structure of the tRNA processing enzyme RNase PH from Aquifex aeolicus.
  J Biol Chem, 278, 32397-32404.
PDB codes: 1udn 1udo 1udq 1uds
12771135 T.Wada, T.Kuzuyama, S.Satoh, S.Kuramitsu, S.Yokoyama, S.Unzai, J.R.Tame, and S.Y.Park (2003).
Crystal structure of 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol kinase, an enzyme in the non-mevalonate pathway of isoprenoid synthesis.
  J Biol Chem, 278, 30022-30027.
PDB code: 1uek
12194989 S.K.Burley, and J.B.Bonanno (2002).
Structuring the universe of proteins.
  Annu Rev Genomics Hum Genet, 3, 243-262.  
11698677 J.B.Bonanno, C.Edo, N.Eswar, U.Pieper, M.J.Romanowski, V.Ilyin, S.E.Gerchman, H.Kycia, F.W.Studier, A.Sali, and S.K.Burley (2001).
Structural genomics of enzymes involved in sterol/isoprenoid biosynthesis.
  Proc Natl Acad Sci U S A, 98, 12896-12901.
PDB codes: 1fi4 1i9a
11406387 S.A.Teichmann, A.G.Murzin, and C.Chothia (2001).
Determination of protein function, evolution and interactions by structural genomics.
  Curr Opin Struct Biol, 11, 354-363.  
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.