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Transferase PDB id
1ll8
Jmol
Contents
Protein chain
114 a.a. *
* Residue conservation analysis
PDB id:
1ll8
Name: Transferase
Title: Structure and interactions of pas kinase n-terminal pas domain: model for intramolecular kinase regulation
Structure: Pas kinase. Chain: a. Fragment: pas-a domain. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
NMR struc: 20 models
Authors: C.A.Amezcua,S.M.Harper,J.Rutter,K.H.Gardner
Key ref:
C.A.Amezcua et al. (2002). Structure and interactions of PAS kinase N-terminal PAS domain: model for intramolecular kinase regulation. Structure, 10, 1349-1361. PubMed id: 12377121 DOI: 10.1016/S0969-2126(02)00857-2
Date:
26-Apr-02     Release date:   09-Oct-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q96RG2  (PASK_HUMAN) -  PAS domain-containing serine/threonine-protein kinase
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1323 a.a.
114 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 6 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: ATP + a protein = ADP + a phosphoprotein
ATP
 + protein
 = ADP
 + phosphoprotein
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     signal transduction   2 terms 
  Biochemical function     signal transducer activity     1 term  

 

 
    reference    
 
 
DOI no: 10.1016/S0969-2126(02)00857-2 Structure 10:1349-1361 (2002)
PubMed id: 12377121  
 
 
Structure and interactions of PAS kinase N-terminal PAS domain: model for intramolecular kinase regulation.
C.A.Amezcua, S.M.Harper, J.Rutter, K.H.Gardner.
 
  ABSTRACT  
 
PAS domains are sensory modules in signal-transducing proteins that control responses to various environmental stimuli. To examine how those domains can regulate a eukaryotic kinase, we have studied the structure and binding interactions of the N-terminal PAS domain of human PAS kinase using solution NMR methods. While this domain adopts a characteristic PAS fold, two regions are unusually flexible in solution. One of these serves as a portal that allows small organic compounds to enter into the core of the domain, while the other binds and inhibits the kinase domain within the same protein. Structural and functional analyses of point mutants demonstrate that the compound and ligand binding regions are linked, suggesting that the PAS domain serves as a ligand-regulated switch for this eukaryotic signaling system.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Structural Features of PAS Domains 		Figure 5.
Figure 5. Identification of the Kinase Binding Site on the Surface of hPASK PAS A
 
  The above figures are reprinted by permission from Cell Press: Structure (2002, 10, 1349-1361) copyright 2002.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21418524 P.Schläfli, J.Tröger, K.Eckhardt, E.Borter, P.Spielmann, and R.H.Wenger (2011).
Substrate preference and phosphatidylinositol monophosphate inhibition of the catalytic domain of the Per-Arnt-Sim domain kinase PASKIN.
  FEBS J, 278, 1757-1768.  
20112293 C.L.Partch, and K.H.Gardner (2010).
Coactivator recruitment: a new role for PAS domains in transcriptional regulation by the bHLH-PAS family.
  J Cell Physiol, 223, 553-557.  
  19715772 V.Poitout, J.Amyot, M.Semache, B.Zarrouki, D.Hagman, and G.Fontés (2010).
Glucolipotoxicity of the pancreatic beta cell.
  Biochim Biophys Acta, 1801, 289-298.  
19502418 G.Fontés, M.Semache, D.K.Hagman, C.Tremblay, R.Shah, C.J.Rhodes, J.Rutter, and V.Poitout (2009).
Involvement of Per-Arnt-Sim Kinase and extracellular-regulated kinases-1/2 in palmitate inhibition of insulin gene expression in pancreatic beta-cells.
  Diabetes, 58, 2048-2058.  
19950993 J.Key, T.H.Scheuermann, P.C.Anderson, V.Daggett, and K.H.Gardner (2009).
Principles of ligand binding within a completely buried cavity in HIF2alpha PAS-B.
  J Am Chem Soc, 131, 17647-17654.
PDB codes: 3h7w 3h82
18974054 L.Corsini, M.Hothorn, G.Stier, V.Rybin, K.Scheffzek, T.J.Gibson, and M.Sattler (2009).
Dimerization and Protein Binding Specificity of the U2AF Homology Motif of the Splicing Factor Puf60.
  J Biol Chem, 284, 630-639.
PDB code: 3dxb
19432806 M.S.Brody, V.Stewart, and C.W.Price (2009).
Bypass suppression analysis maps the signalling pathway within a multidomain protein: the RsbP energy stress phosphatase 2C from Bacillus subtilis.
  Mol Microbiol, 72, 1221-1234.  
19129502 T.H.Scheuermann, D.R.Tomchick, M.Machius, Y.Guo, R.K.Bruick, and K.H.Gardner (2009).
Artificial ligand binding within the HIF2alpha PAS-B domain of the HIF2 transcription factor.
  Proc Natl Acad Sci U S A, 106, 450-455.
PDB codes: 3f1n 3f1o 3f1p
18782776 A.K.Sharma, G.P.Zhou, J.Kupferman, H.K.Surks, E.N.Christensen, J.J.Chou, M.E.Mendelsohn, and A.C.Rigby (2008).
Probing the Interaction between the Coiled Coil Leucine Zipper of cGMP-dependent Protein Kinase I{alpha} and the C Terminus of the Myosin Binding Subunit of the Myosin Light Chain Phosphatase.
  J Biol Chem, 283, 32860-32869.  
18827010 F.J.Tan, M.Husain, C.M.Manlandro, M.Koppenol, A.Z.Fire, and R.B.Hill (2008).
CED-9 and mitochondrial homeostasis in C. elegans muscle.
  J Cell Sci, 121, 3373-3382.  
18344204 H.X.Hao, and J.Rutter (2008).
The role of PAS kinase in regulating energy metabolism.
  IUBMB Life, 60, 204-209.  
18203838 K.J.Watts, M.S.Johnson, and B.L.Taylor (2008).
Structure-function relationships in the HAMP and proximal signaling domains of the aerotaxis receptor Aer.
  J Bacteriol, 190, 2118-2127.  
18006497 X.Ma, N.Sayed, P.Baskaran, A.Beuve, and F.van den Akker (2008).
PAS-mediated dimerization of soluble guanylyl cyclase revealed by signal transduction histidine kinase domain crystal structure.
  J Biol Chem, 283, 1167-1178.
PDB codes: 2p04 2p08
17550789 D.A.Landfried, D.A.Vuletich, M.P.Pond, and J.T.Lecomte (2007).
Structural and thermodynamic consequences of b heme binding for monomeric apoglobins and other apoproteins.
  Gene, 398, 12-28.  
17989693 J.H.Grose, T.L.Smith, H.Sabic, and J.Rutter (2007).
Yeast PAS kinase coordinates glucose partitioning in response to metabolic and cell integrity signaling.
  EMBO J, 26, 4824-4830.  
17067285 J.M.Christie (2007).
Phototropin blue-light receptors.
  Annu Rev Plant Biol, 58, 21-45.  
16759348 E.Swinnen, V.Wanke, J.Roosen, B.Smets, F.Dubouloz, I.Pedruzzi, E.Cameroni, C.De Virgilio, and J.Winderickx (2006).
Rim15 and the crossroads of nutrient signalling pathways in Saccharomyces cerevisiae.
  Cell Div, 1, 3.  
16385002 G.R.Thuduppathy, and R.B.Hill (2006).
Acid destabilization of the solution conformation of Bcl-xL does not drive its pH-dependent insertion into membranes.
  Protein Sci, 15, 248-257.  
16877709 M.L.Cheever, T.G.Kutateladze, and M.Overduin (2006).
Increased mobility in the membrane targeting PX domain induced by phosphatidylinositol 3-phosphate.
  Protein Sci, 15, 1873-1882.  
16908530 N.Latysheva, G.Muratov, S.Rajesh, M.Padgett, N.A.Hotchin, M.Overduin, and F.Berditchevski (2006).
Syntenin-1 is a new component of tetraspanin-enriched microdomains: mechanisms and consequences of the interaction of syntenin-1 with CD63.
  Mol Cell Biol, 26, 7707-7718.  
16704425 Y.Mukaiyama, T.Uchida, E.Sato, A.Sasaki, Y.Sato, J.Igarashi, H.Kurokawa, I.Sagami, T.Kitagawa, and T.Shimizu (2006).
Spectroscopic and DNA-binding characterization of the isolated heme-bound basic helix-loop-helix-PAS-A domain of neuronal PAS protein 2 (NPAS2), a transcription activator protein associated with circadian rhythms.
  FEBS J, 273, 2528-2539.  
16195543 C.L.Gustafson, C.V.Stauffacher, K.Hallenga, and R.L.Van Etten (2005).
Solution structure of the low-molecular-weight protein tyrosine phosphatase from Tritrichomonas foetus reveals a flexible phosphate binding loop.
  Protein Sci, 14, 2515-2525.
PDB code: 1p8a
16129688 J.Yang, L.Zhang, P.J.Erbel, K.H.Gardner, K.Ding, J.A.Garcia, and R.K.Bruick (2005).
Functions of the Per/ARNT/Sim domains of the hypoxia-inducible factor.
  J Biol Chem, 280, 36047-36054.  
15654897 M.Nakasako, T.Iwata, K.Inoue, and S.Tokutomi (2005).
Light-induced global structural changes in phytochrome A regulating photomorphogenesis in plants.
  FEBS J, 272, 603-612.  
15629718 O.Yildiz, M.Doi, I.Yujnovsky, L.Cardone, A.Berndt, S.Hennig, S.Schulze, C.Urbanke, P.Sassone-Corsi, and E.Wolf (2005).
Crystal structure and interactions of the PAS repeat region of the Drosophila clock protein PERIOD.
  Mol Cell, 17, 69-82.
PDB code: 1wa9
15936961 R.H.Wenger, and D.M.Katschinski (2005).
The hypoxic testis and post-meiotic expression of PAS domain proteins.
  Semin Cell Dev Biol, 16, 547-553.  
16098197 R.Koudo, H.Kurokawa, E.Sato, J.Igarashi, T.Uchida, I.Sagami, T.Kitagawa, and T.Shimizu (2005).
Spectroscopic characterization of the isolated heme-bound PAS-B domain of neuronal PAS domain protein 2 associated with circadian rhythms.
  FEBS J, 272, 4153-4162.  
14638687 A.Chapman-Smith, J.K.Lutwyche, and M.L.Whitelaw (2004).
Contribution of the Per/Arnt/Sim (PAS) domains to DNA binding by the basic helix-loop-helix PAS transcriptional regulators.
  J Biol Chem, 279, 5353-5362.  
15009198 M.H.Hefti, K.J.Françoijs, S.C.de Vries, R.Dixon, and J.Vervoort (2004).
The PAS fold. A redefinition of the PAS domain based upon structural prediction.
  Eur J Biochem, 271, 1198-1208.  
15373839 M.Watanabe, H.Kurokawa, T.Yoshimura-Suzuki, I.Sagami, and T.Shimizu (2004).
Critical roles of Asp40 at the haem proximal side of haem-regulated phosphodiesterase from Escherichia coli in redox potential, auto-oxidation and catalytic control.
  Eur J Biochem, 271, 3937-3942.  
  14643885 R.J.Kewley, M.L.Whitelaw, and A.Chapman-Smith (2004).
The mammalian basic helix-loop-helix/PAS family of transcriptional regulators.
  Int J Biochem Cell Biol, 36, 189-204.  
14612459 S.Taguchi, T.Matsui, J.Igarashi, Y.Sasakura, Y.Araki, O.Ito, S.Sugiyama, I.Sagami, and T.Shimizu (2004).
Binding of oxygen and carbon monoxide to a heme-regulated phosphodiesterase from Escherichia coli. Kinetics and infrared spectra of the full-length wild-type enzyme, isolated PAS domain, and Met-95 mutants.
  J Biol Chem, 279, 3340-3347.  
12972598 D.M.Katschinski, H.H.Marti, K.F.Wagner, J.Shibata, K.Eckhardt, F.Martin, R.Depping, U.Paasch, M.Gassmann, B.Ledermann, I.Desbaillets, and R.H.Wenger (2003).
Targeted disruption of the mouse PAS domain serine/threonine kinase PASKIN.
  Mol Cell Biol, 23, 6780-6789.  
  14572542 L.Aravind, V.Anantharaman, and L.M.Iyer (2003).
Evolutionary connections between bacterial and eukaryotic signaling systems: a genomic perspective.
  Curr Opin Microbiol, 6, 490-497.  
12815340 M.Machius (2003).
Structural biology: a high-tech tool for biomedical research.
  Curr Opin Nephrol Hypertens, 12, 431-438.  
12970567 S.M.Harper, L.C.Neil, and K.H.Gardner (2003).
Structural basis of a phototropin light switch.
  Science, 301, 1541-1544.  
12563032 S.Rajagopal, and K.Moffat (2003).
Crystal structure of a photoactive yellow protein from a sensor histidine kinase: conformational variability and signal transduction.
  Proc Natl Acad Sci U S A, 100, 1649-1654.
PDB code: 1mzu
12867417 S.Reinelt, E.Hofmann, T.Gerharz, M.Bott, and D.R.Madden (2003).
The structure of the periplasmic ligand-binding domain of the sensor kinase CitA reveals the first extracellular PAS domain.
  J Biol Chem, 278, 39189-39196.
PDB code: 1p0z
14551206 T.Yoshimura, I.Sagami, Y.Sasakura, and T.Shimizu (2003).
Relationships between heme incorporation, tetramer formation, and catalysis of a heme-regulated phosphodiesterase from Escherichia coli: a study of deletion and site-directed mutants.
  J Biol Chem, 278, 53105-53111.  
  12445766 E.D.Getzoff (2002).
PASsing a signal: low carbs, less protein.
  Chem Biol, 9, 1165-1166.  
12446832 E.M.Dioum, J.Rutter, J.R.Tuckerman, G.Gonzalez, M.A.Gilles-Gonzalez, and S.L.McKnight (2002).
NPAS2: a gas-responsive transcription factor.
  Science, 298, 2385-2387.  
12372297 J.Rutter, B.L.Probst, and S.L.McKnight (2002).
Coordinate regulation of sugar flux and translation by PAS kinase.
  Cell, 111, 17-28.  
12408859 W.A.Wilson, and P.J.Roach (2002).
Nutrient-regulated protein kinases in budding yeast.
  Cell, 111, 155-158.  
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.