PDBsum entry 1mzj

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Transferase PDB id
Protein chains
334 a.a. *
Waters ×379
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystal structure of the priming beta-ketosynthase from the r1128 polyketide biosynthetic pathway
Structure: Beta-ketoacylsynthase iii. Chain: a, b. Synonym: beta-ketosynthase. Engineered: yes
Source: Streptomyces sp. R1128. Organism_taxid: 140437. Gene: zhuh. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dimer (from PQS)
2.10Å     R-factor:   0.215     R-free:   0.251
Authors: H.Pan,S.C.Tsai,E.S.Meadows,L.J.W.Miercke,A.Keatinge-Clay, J.O'Connell,C.Khosla,R.M.Stroud
Key ref:
C.E.Dann et al. (2002). Structure of factor-inhibiting hypoxia-inducible factor 1: An asparaginyl hydroxylase involved in the hypoxic response pathway. Proc Natl Acad Sci U S A, 99, 15351-15356. PubMed id: 12432100 DOI: 10.1073/pnas.202614999
08-Oct-02     Release date:   11-Dec-02    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q9F6D4  (FABH_STRLI) -  3-oxoacyl-[acyl-carrier-protein] synthase 3
339 a.a.
334 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Beta-ketoacyl-[acyl-carrier-protein] synthase Iii.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Acetyl-CoA + malonyl-[acyl-carrier-protein] = acetoacetyl-[acyl-carrier- protein] + CoA + CO2
Bound ligand (Het Group name = COA)
matches with 94.00% similarity
+ malonyl-[acyl-carrier-protein]
= acetoacetyl-[acyl-carrier- protein]
+ CoA
Bound ligand (Het Group name = ACE)
matches with 50.00% similarity
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     metabolic process   5 terms 
  Biochemical function     catalytic activity     6 terms  


DOI no: 10.1073/pnas.202614999 Proc Natl Acad Sci U S A 99:15351-15356 (2002)
PubMed id: 12432100  
Structure of factor-inhibiting hypoxia-inducible factor 1: An asparaginyl hydroxylase involved in the hypoxic response pathway.
C.E.Dann, R.K.Bruick, J.Deisenhofer.
Precise regulation of the evolutionarily conserved hypoxia-inducible transcription factor (HIF) ensures proper adaptation to variations in oxygen availability throughout development and into adulthood. Oxygen-dependent regulation of HIF stability and activity are mediated by hydroxylation of conserved proline and asparagine residues, respectively. Because the relevant prolyl and asparginyl hydroxylases use O(2) to effect these posttranslational modifications, these enzymes are implicated as direct oxygen sensors in the mammalian hypoxic response pathway. Here we present the structure of factor-inhibiting HIF-1 (FIH-1), the pertinent asparaginyl hydroxylase involved in hypoxic signaling. Hydroxylation of the C-terminal transactivation domain (CTAD) of HIF by FIH-1 prevents CTAD association with transcriptional coactivators under normoxic conditions. Consistent with other structurally known hydroxylases, FIH-1 is comprised of a beta-strand jellyroll core with both Fe(II) and the cosubstrate 2-oxoglutarate bound in the active site. Details of the molecular contacts at the active site of FIH-1 have been elucidated and provide a platform for future drug design. Furthermore, the structure reveals the presence of a FIH-1 homodimer that forms in solution and is essential for FIH activity.
  Selected figure(s)  
Figure 2.
Fig 2. The primary structure of FIH-1 is labeled with secondary structure elements taken from the x-ray crystallographic model. -strands and helices are depicted as red arrows and yellow boxes, respectively. Residues responsible for Fe(II) binding are highlighted in red, whereas residues in close contact with 2-OG are highlighted in green.
Figure 3.
Fig 3. FIH-1 structure contains a -jellyroll core marked by an extension of one of the -sheets away from the core and helices dotting the periphery. (A) A ribbon model of the FIH-1 monomer is positioned looking between the -sheets comprising the jellyroll and into the active site cavity. The active site metal is shown as a red sphere. Structural elements are colored as in Fig. 2. (B) A secondary structure topology diagram shows the arrangement of the 14 -strands (triangles) and 8 helices (circles) in FIH-1. The core jellyroll motif, structurally homologous to the cupin protein family, is colored in red. (C) FIH-1 exists as a functionally relevant dimer in the crystal. The first monomer of the dimer is colored as in A, whereas the second monomer is blue. N and C termini are marked as black circles. The figure was generated by using RIBBONS (41).
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21443853 E.Saban, S.C.Flagg, and M.J.Knapp (2011).
Uncoupled O2-activation in the human HIF-asparaginyl hydroxylase, FIH, does not produce reactive oxygen species.
  J Inorg Biochem, 105, 630-636.  
20972222 M.Kato, Y.Araiso, A.Noma, A.Nagao, T.Suzuki, R.Ishitani, and O.Nureki (2011).
Crystal structure of a novel JmjC-domain-containing protein, TYW5, involved in tRNA modification.
  Nucleic Acids Res, 39, 1576-1585.
PDB codes: 3al5 3al6
20396966 H.Moon, S.Han, H.Park, and J.Choe (2010).
Crystal structures of human FIH-1 in complex with quinol family inhibitors.
  Mol Cells, 29, 471-474.
PDB codes: 3kcx 3kcy
20040577 H.S.Kim, H.L.Kim, K.H.Kim, d.o. .J.Kim, S.J.Lee, J.Y.Yoon, H.J.Yoon, H.Y.Lee, S.B.Park, S.J.Kim, J.Y.Lee, and S.W.Suh (2010).
Crystal structure of Tpa1 from Saccharomyces cerevisiae, a component of the messenger ribonucleoprotein complex.
  Nucleic Acids Res, 38, 2099-2110.
PDB codes: 3kt1 3kt4 3kt7
20512927 J.C.Hsieh, S.A.Slater, G.K.Whitfield, J.L.Dawson, G.Hsieh, C.Sheedy, C.A.Haussler, and M.R.Haussler (2010).
Analysis of hairless corepressor mutants to characterize molecular cooperation with the vitamin D receptor in promoting the mammalian hair cycle.
  J Cell Biochem, 110, 671-686.  
20679243 X.Hong, J.Zang, J.White, C.Wang, C.H.Pan, R.Zhao, R.C.Murphy, S.Dai, P.Henson, J.W.Kappler, J.Hagman, and G.Zhang (2010).
Interaction of JMJD6 with single-stranded RNA.
  Proc Natl Acad Sci U S A, 107, 14568-14572.
PDB codes: 3ld8 3ldb
19096759 H.Chen, and M.Costa (2009).
Iron- and 2-oxoglutarate-dependent dioxygenases: an emerging group of molecular targets for nickel toxicity and carcinogenicity.
  Biometals, 22, 191-196.  
19561615 M.Okamoto, M.Van Stry, L.Chung, M.Koyanagi, X.Sun, Y.Suzuki, O.Ohara, H.Kitamura, A.Hijikata, M.Kubo, and M.Bix (2009).
Mina, an Il4 repressor, controls T helper type 2 bias.
  Nat Immunol, 10, 872-879.  
19726677 T.Sakamoto, and M.Seiki (2009).
Mint3 enhances the activity of hypoxia-inducible factor-1 (HIF-1) in macrophages by suppressing the activity of factor inhibiting HIF-1.
  J Biol Chem, 284, 30350-30359.  
18391407 B.Lohkamp, and D.Dobritzsch (2008).
A mixture of fortunes: the curious determination of the structure of Escherichia coli BL21 Gab protein.
  Acta Crystallogr D Biol Crystallogr, 64, 407-415.
PDB code: 2r6s
18174379 D.H.Shin, Y.S.Chun, D.S.Lee, L.E.Huang, and J.W.Park (2008).
Bortezomib inhibits tumor adaptation to hypoxia by stimulating the FIH-mediated repression of hypoxia-inducible factor-1.
  Blood, 111, 3131-3136.  
18813363 J.M.Simmons, T.A.Müller, and R.P.Hausinger (2008).
Fe(II)/alpha-ketoglutarate hydroxylases involved in nucleobase, nucleoside, nucleotide, and chromatin metabolism.
  Dalton Trans, (), 5132-5142.  
18564434 P.Hahn, J.Böse, S.Edler, and A.Lengeling (2008).
Genomic structure and expression of Jmjd6 and evolutionary analysis in the context of related JmjC domain containing proteins.
  BMC Genomics, 9, 293.  
18568157 R.Chowdhury, A.Hardy, and C.J.Schofield (2008).
The human oxygen sensing machinery and its manipulation.
  Chem Soc Rev, 37, 1308-1319.  
18805587 Y.H.Chen, L.M.Comeaux, R.W.Herbst, E.Saban, D.C.Kennedy, M.J.Maroney, and M.J.Knapp (2008).
Coordination changes and auto-hydroxylation of FIH-1: uncoupled O2-activation in a human hypoxia sensor.
  J Inorg Biochem, 102, 2120-2129.  
17292925 A.B.Johnson, and M.C.Barton (2007).
Hypoxia-induced and stress-specific changes in chromatin structure and function.
  Mutat Res, 618, 149-162.  
17301803 A.Ozer, and R.K.Bruick (2007).
Non-heme dioxygenases: cellular sensors and regulators jelly rolled into one?
  Nat Chem Biol, 3, 144-153.  
17947579 B.Chang, Y.Chen, Y.Zhao, and R.K.Bruick (2007).
JMJD6 is a histone arginine demethylase.
  Science, 318, 444-447.  
17682059 J.Li, E.Wang, S.Dutta, J.S.Lau, S.W.Jiang, K.Datta, and D.Mukhopadhyay (2007).
Protein kinase C-mediated modulation of FIH-1 expression by the homeodomain protein CDP/Cut/Cux.
  Mol Cell Biol, 27, 7345-7353.  
17220275 Q.Yan, S.Bartz, M.Mao, L.Li, and W.G.Kaelin (2007).
The hypoxia-inducible factor 2alpha N-terminal and C-terminal transactivation domains cooperate to promote renal tumorigenesis in vivo.
  Mol Cell Biol, 27, 2092-2102.  
17431691 V.Purpero, and G.R.Moran (2007).
The diverse and pervasive chemistries of the alpha-keto acid dependent enzymes.
  J Biol Inorg Chem, 12, 587-601.  
16880954 J.L.Anderson, and S.K.Chapman (2006).
Molecular mechanisms of enzyme-catalysed halogenation.
  Mol Biosyst, 2, 350-357.  
16320009 K.D.Koehntop, S.Marimanikkuppam, M.J.Ryle, R.P.Hausinger, and L.Que (2006).
Self-hydroxylation of taurine/alpha-ketoglutarate dioxygenase: evidence for more than one oxygen activation mechanism.
  J Biol Inorg Chem, 11, 63-72.  
16541079 L.C.Blasiak, F.H.Vaillancourt, C.T.Walsh, and C.L.Drennan (2006).
Crystal structure of the non-haem iron halogenase SyrB2 in syringomycin biosynthesis.
  Nature, 440, 368-371.
PDB codes: 2fct 2fcu 2fcv
16782814 M.A.McDonough, V.Li, E.Flashman, R.Chowdhury, C.Mohr, B.M.Liénard, J.Zondlo, N.J.Oldham, I.J.Clifton, J.Lewis, L.A.McNeill, R.J.Kurzeja, K.S.Hewitson, E.Yang, S.Jordan, R.S.Syed, and C.J.Schofield (2006).
Cellular oxygen sensing: Crystal structure of hypoxia-inducible factor prolyl hydroxylase (PHD2).
  Proc Natl Acad Sci U S A, 103, 9814-9819.
PDB codes: 2g19 2g1m
16762840 M.Zofall, and S.I.Grewal (2006).
Swi6/HP1 recruits a JmjC domain protein to facilitate transcription of heterochromatic repeats.
  Mol Cell, 22, 681-692.  
16983801 R.J.Klose, E.M.Kallin, and Y.Zhang (2006).
JmjC-domain-containing proteins and histone demethylation.
  Nat Rev Genet, 7, 715-727.  
16731970 T.A.Müller, M.I.Zavodszky, M.Feig, L.A.Kuhn, and R.P.Hausinger (2006).
Structural basis for the enantiospecificities of R- and S-specific phenoxypropionate/alpha-ketoglutarate dioxygenases.
  Protein Sci, 15, 1356-1368.  
15738986 H.J.Dyson, and P.E.Wright (2005).
Intrinsically unstructured proteins and their functions.
  Nat Rev Mol Cell Biol, 6, 197-208.  
15122348 C.J.Schofield, and P.J.Ratcliffe (2004).
Oxygen sensing by HIF hydroxylases.
  Nat Rev Mol Cell Biol, 5, 343-354.  
15134335 E.Metzen, and P.J.Ratcliffe (2004).
HIF hydroxylation and cellular oxygen sensing.
  Biol Chem, 385, 223-230.  
14730595 J.H.Distler, R.H.Wenger, M.Gassmann, M.Kurowska, A.Hirth, S.Gay, and O.Distler (2004).
Physiologic responses to hypoxia and implications for hypoxia-inducible factors in the pathogenesis of rheumatoid arthritis.
  Arthritis Rheum, 50, 10-23.  
14983005 K.Ginalski, L.Rychlewski, D.Baker, and N.V.Grishin (2004).
Protein structure prediction for the male-specific region of the human Y chromosome.
  Proc Natl Acad Sci U S A, 101, 2305-2310.  
15341784 K.S.Hewitson, and C.J.Schofield (2004).
The HIF pathway as a therapeutic target.
  Drug Discov Today, 9, 704-711.  
14718929 K.Valegård, A.C.Terwisscha van Scheltinga, A.Dubus, G.Ranghino, L.M.Oster, J.Hajdu, and I.Andersson (2004).
The structural basis of cephalosporin formation in a mononuclear ferrous enzyme.
  Nat Struct Mol Biol, 11, 95.
PDB codes: 1unb 1uo9 1uob 1uof 1uog
15193161 M.Cikala, O.Alexandrova, C.N.David, M.Pröschel, B.Stiening, P.Cramer, and A.Böttger (2004).
The phosphatidylserine receptor from Hydra is a nuclear protein with potential Fe(II) dependent oxygenase activity.
  BMC Cell Biol, 5, 26.  
15468961 W.Jelkmann (2004).
Molecular biology of erythropoietin.
  Intern Med, 43, 649-659.  
15489165 Z.Zhang, J.S.Ren, I.J.Clifton, and C.J.Schofield (2004).
Crystal structure and mechanistic implications of 1-aminocyclopropane-1-carboxylic acid oxidase--the ethylene-forming enzyme.
  Chem Biol, 11, 1383-1394.
PDB codes: 1w9y 1wa6
13678535 N.Goda, S.J.Dozier, and R.S.Johnson (2003).
HIF-1 in cell cycle regulation, apoptosis, and tumor progression.
  Antioxid Redox Signal, 5, 467-473.  
12825087 S.Bhattacharya, and P.J.Ratcliffe (2003).
ExCITED about HIF.
  Nat Struct Biol, 10, 501-503.  
12778114 S.J.Freedman, Z.Y.Sun, A.L.Kung, D.S.France, G.Wagner, and M.J.Eck (2003).
Structural basis for negative regulation of hypoxia-inducible factor-1alpha by CITED2.
  Nat Struct Biol, 10, 504-512.
PDB code: 1p4q
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.