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PDBsum entry 1qgx

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protein ligands metals links
Hydrolase PDB id
1qgx
Jmol
Contents
Protein chain
354 a.a. *
Ligands
PO4
SO4
AMP
BME
Metals
_MG ×2
Waters ×377
* Residue conservation analysis
PDB id:
1qgx
Name: Hydrolase
Title: X-ray structure of yeast hal2p
Structure: 3',5'-adenosine bisphosphatase. Chain: a. Synonym: pap phosphatase. Engineered: yes. Other_details: complexed with amp
Source: Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Expressed in: saccharomyces cerevisiae. Expression_system_taxid: 4932
Resolution:
1.60Å     R-factor:   0.197     R-free:   0.235
Authors: A.Albert,L.Yenush,M.R.Gil-Mascarell,P.L.Rodriguez,J.Patel, M.Martinez-Ripoll,T.L.Blundell,R.Serrano
Key ref:
A.Albert et al. (2000). X-ray structure of yeast Hal2p, a major target of lithium and sodium toxicity, and identification of framework interactions determining cation sensitivity. J Mol Biol, 295, 927-938. PubMed id: 10656801 DOI: 10.1006/jmbi.1999.3408
Date:
10-May-99     Release date:   04-Jan-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P32179  (MET22_YEAST) -  3'(2'),5'-bisphosphate nucleotidase
Seq:
Struc:
357 a.a.
354 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.1.3.7  - 3'(2'),5'-bisphosphate nucleotidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Adenosine 3',5'-bisphosphate + H2O = adenosine 5'-phosphate + phosphate
Adenosine 3',5'-bisphosphate
+ H(2)O
=
adenosine 5'-phosphate
Bound ligand (Het Group name = AMP)
corresponds exactly
+
phosphate
Bound ligand (Het Group name = PO4)
corresponds exactly
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cellular_component   3 terms 
  Biological process     response to stress   7 terms 
  Biochemical function     hydrolase activity     3 terms  

 

 
    reference    
 
 
DOI no: 10.1006/jmbi.1999.3408 J Mol Biol 295:927-938 (2000)
PubMed id: 10656801  
 
 
X-ray structure of yeast Hal2p, a major target of lithium and sodium toxicity, and identification of framework interactions determining cation sensitivity.
A.Albert, L.Yenush, M.R.Gil-Mascarell, P.L.Rodriguez, S.Patel, M.Martínez-Ripoll, T.L.Blundell, R.Serrano.
 
  ABSTRACT  
 
The product of the yeast HAL2 gene (Hal2p) is an in vivo target of sodium and lithium toxicity and its overexpression improves salt tolerance in yeast and plants. Hal2p is a metabolic phosphatase which catalyses the hydrolysis of 3'-phosphoadenosine-5'-phosphate (PAP) to AMP. It is, the prototype of an evolutionarily conserved family of PAP phosphatases and the engineering of sodium insensitive enzymes of this group may contribute to the generation of salt-tolerant crops. We have solved the crystal structure of Hal2p in complex with magnesium, lithium and the two products of PAP hydrolysis, AMP and Pi, at 1.6 A resolution. A functional screening of random mutations of the HAL2 gene in growing yeast generated forms of the enzyme with reduced cation sensitivity. Analysis of these mutants defined a salt bridge (Glu238 ellipsis Arg152) and a hydrophobic bond (Va170 ellipsis Trp293) as important framework interactions determining cation sensitivity. Hal2p belongs to a larger superfamily of lithium-sensitive phosphatases which includes inositol monophosphatase. The hydrophobic interaction mutated in Hal2p is conserved in this superfamily and its disruption in human inositol monophosphatase also resulted in reduced cation sensitivity.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. (a) Ribbon representation of Hal2p structure. Magnesium atoms are displayed in gray, AMP and Pi are displayed in CPK mode. (b) Schematic representation of Hal2p showing all the secondary structural elements and binding sites. Continuous lines and broken lines represent conserved or non-conserved secondary structural elements among the sugar enzymes structural class; A is adenosine ring binding site and P is AMP, P5' binding site. (c) Active site in Hal2p. A view of the metal binding sites (distances are in Å). (d) PAP binding site.
Figure 4.
Figure 4. (a) A diagram showing the superposition of Hal2p (thick yellow C^a trace) and human inositol monophosphatase (thin cyan C^a trace); the Figure shows the hydrogen bonding network involving Asp145 and the salt bridge Arg152 Asp263, linking a5 and the loop between b9 and a7. (b) A detail of this salt bridge and (c) a section of Hal2p structure showing where the point mutation V70A is located. Point mutations are highlighted, distances are in Å.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2000, 295, 927-938) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20975943 H.M.Jaag, and P.D.Nagy (2010).
The combined effect of environmental and host factors on the emergence of viral RNA recombinants.
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20331428 S.Y.Lu, G.R.Zhao, A.M.Wu, M.A.Jenks, S.Zhang, and J.Y.Liu (2010).
Molecular cloning of a cotton phosphatase gene and its functional characterization.
  Biochemistry (Mosc), 75, 85-94.  
20027624 Z.Li, K.A.Stieglitz, A.L.Shrout, Y.Wei, R.M.Weis, B.Stec, and M.F.Roberts (2010).
Mobile loop mutations in an archaeal inositol monophosphatase: modulating three-metal ion assisted catalysis and lithium inhibition.
  Protein Sci, 19, 309-318.  
19073594 G.Brown, A.Singer, V.V.Lunin, M.Proudfoot, T.Skarina, R.Flick, S.Kochinyan, R.Sanishvili, A.Joachimiak, A.M.Edwards, A.Savchenko, and A.F.Yakunin (2009).
Structural and Biochemical Characterization of the Type II Fructose-1,6-bisphosphatase GlpX from Escherichia coli.
  J Biol Chem, 284, 3784-3792.
PDB codes: 1ni9 3big 3bih 3d1r
18780819 M.Brucet, J.Querol-Audí, K.Bertlik, J.Lloberas, I.Fita, and A.Celada (2008).
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  Protein Sci, 17, 2059-2069.
PDB codes: 3b6o 3b6p
18454554 S.K.Hatzios, A.T.Iavarone, and C.R.Bertozzi (2008).
Rv2131c from Mycobacterium tuberculosis is a CysQ 3'-phosphoadenosine-5'-phosphatase.
  Biochemistry, 47, 5823-5831.  
17725819 A.K.Brown, G.Meng, H.Ghadbane, D.J.Scott, L.G.Dover, J.Nigou, G.S.Besra, and K.Fütterer (2007).
Dimerization of inositol monophosphatase Mycobacterium tuberculosis SuhB is not constitutive, but induced by binding of the activator Mg2+.
  BMC Struct Biol, 7, 55.
PDB code: 2q74
17450323 J.J.Cheong, I.Hwang, S.Rhee, T.W.Moon, Y.D.Choi, and H.B.Kwon (2007).
Complementation of an E. coli cysteine auxotrophic mutant for the structural modification study of 3'(2'),5'-bisphosphate nucleotidase.
  Biotechnol Lett, 29, 913-918.  
16352596 A.L.Todeschini, C.Condon, and L.Bénard (2006).
Sodium-induced GCN4 expression controls the accumulation of the 5' to 3' RNA degradation inhibitor, 3'-phosphoadenosine 5'-phosphate.
  J Biol Chem, 281, 3276-3282.  
16391050 J.Y.Zhang, J.Zou, Q.Bao, W.L.Chen, L.Wang, H.Yang, and C.C.Zhang (2006).
A lithium-sensitive and sodium-tolerant 3'-phosphoadenosine-5'-phosphatase encoded by halA from the cyanobacterium Arthrospira platensis is closely related to its counterparts from yeasts and plants.
  Appl Environ Microbiol, 72, 245-251.  
16467467 M.Aggarwal, and A.K.Mondal (2006).
Role of N-terminal hydrophobic region in modulating the subcellular localization and enzyme activity of the bisphosphate nucleotidase from Debaryomyces hansenii.
  Eukaryot Cell, 5, 262-271.  
15870269 L.Y.Wang, K.Shimada, M.Morishita, and K.Shiozaki (2005).
Response of fission yeast to toxic cations involves cooperative action of the stress-activated protein kinase Spc1/Sty1 and the Hal4 protein kinase.
  Mol Cell Biol, 25, 3945-3955.  
15849794 M.Aggarwal, P.K.Bansal, and A.K.Mondal (2005).
Molecular cloning and biochemical characterization of a 3'(2'),5'-bisphosphate nucleotidase from Debaryomyces hansenii.
  Yeast, 22, 457-470.  
15684411 N.P.Shull, S.L.Spinelli, and E.M.Phizicky (2005).
A highly specific phosphatase that acts on ADP-ribose 1''-phosphate, a metabolite of tRNA splicing in Saccharomyces cerevisiae.
  Nucleic Acids Res, 33, 650-660.  
15858264 R.Gill, F.Mohammed, R.Badyal, L.Coates, P.Erskine, D.Thompson, J.Cooper, M.Gore, and S.Wood (2005).
High-resolution structure of myo-inositol monophosphatase, the putative target of lithium therapy.
  Acta Crystallogr D Biol Crystallogr, 61, 545-555.
PDB code: 2bji
15500469 L.Xiong, H.Lee, R.Huang, and J.K.Zhu (2004).
A single amino acid substitution in the Arabidopsis FIERY1/HOS2 protein confers cold signaling specificity and lithium tolerance.
  Plant J, 40, 536-545.  
11940584 K.A.Stieglitz, K.A.Johnson, H.Yang, M.F.Roberts, B.A.Seaton, J.F.Head, and B.Stec (2002).
Crystal structure of a dual activity IMPase/FBPase (AF2372) from Archaeoglobus fulgidus. The story of a mobile loop.
  J Biol Chem, 277, 22863-22874.
PDB codes: 1lbv 1lbw 1lbx 1lby 1lbz
11867520 L.Yenush, J.M.Mulet, J.Ariño, and R.Serrano (2002).
The Ppz protein phosphatases are key regulators of K+ and pH homeostasis: implications for salt tolerance, cell wall integrity and cell cycle progression.
  EMBO J, 21, 920-929.  
11432986 A.Mora, G.Sabio, R.A.González-Polo, A.Cuenda, D.R.Alessi, J.C.Alonso, J.M.Fuentes, G.Soler, and F.Centeno (2001).
Lithium inhibits caspase 3 activation and dephosphorylation of PKB and GSK3 induced by K+ deprivation in cerebellar granule cells.
  J Neurochem, 78, 199-206.  
11264477 C.J.Phiel, and P.S.Klein (2001).
Molecular targets of lithium action.
  Annu Rev Pharmacol Toxicol, 41, 789-813.  
11454443 R.Serrano, and A.Rodriguez-Navarro (2001).
Ion homeostasis during salt stress in plants.
  Curr Opin Cell Biol, 13, 399-404.  
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.