PDBsum entry 1xnj

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Transferase PDB id
Protein chain
590 a.a. *
ADX ×3
Waters ×667
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Aps complex of human paps synthetase 1
Structure: Bifunctional 3'-phosphoadenosine 5'-phosphosulfat synthetase 1. Chain: b, a. Synonym: paps synthetase 1, papss 1, sulfurylase kinase 1, engineered: yes. Other_details: [includes: sulfate adenylyltransferase (sulf adenylate transferase, sat, atp-sulfurylase. Adenylyl-sulfa (adenylylsulfate 3'-phosphotransferase, aps kinase, adenosi phosphosulfate 3'-phosphotransferase, 3'-phosphoadenosine-5
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: papss1, papss, atpsk1. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Biol. unit: Dimer (from PQS)
1.98Å     R-factor:   0.187     R-free:   0.239
Authors: S.Harjes,P.Bayer,A.J.Scheidig
Key ref:
S.Harjes et al. (2005). The crystal structure of human PAPS synthetase 1 reveals asymmetry in substrate binding. J Mol Biol, 347, 623-635. PubMed id: 15755455 DOI: 10.1016/j.jmb.2005.01.005
05-Oct-04     Release date:   30-Aug-05    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
O43252  (PAPS1_HUMAN) -  Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 1
624 a.a.
590 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class 2: E.C.  - Adenylyl-sulfate kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + adenylyl sulfate = ADP + 3'-phosphoadenylyl sulfate
adenylyl sulfate
Bound ligand (Het Group name = ADX)
corresponds exactly
Bound ligand (Het Group name = ADP)
corresponds exactly
+ 3'-phosphoadenylyl sulfate
   Enzyme class 3: E.C.  - Sulfate adenylyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + sulfate = diphosphate + adenylyl sulfate
Bound ligand (Het Group name = ADP)
matches with 87.10% similarity
+ sulfate
= diphosphate
adenylyl sulfate
Bound ligand (Het Group name = ADX)
corresponds exactly
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!
  Cellular component     cytosol   1 term 
  Biological process     metabolic process   10 terms 
  Biochemical function     catalytic activity     8 terms  


DOI no: 10.1016/j.jmb.2005.01.005 J Mol Biol 347:623-635 (2005)
PubMed id: 15755455  
The crystal structure of human PAPS synthetase 1 reveals asymmetry in substrate binding.
S.Harjes, P.Bayer, A.J.Scheidig.
The high energy sulfate donor 3'-phosphoadenosine-5-phosphosulfate (PAPS) is used for sulfate conjugation of extracellular matrix, hormones and drugs. Human PAPS synthetase 1 catalyzes two subsequent reactions starting from ATP and sulfate. First the ATP sulfurylase domain forms APS, then the APS kinase domain phosphorylates the APS intermediate to PAPS. Up to now the interaction between the two enzymatic activities remained elusive, mainly because of missing structural information. Here we present the crystal structure of human PAPSS1 at 1.8 angstroms resolution. The structure reveals a homodimeric, asymmetric complex with the shape of a chair. The two kinase domains adopt different conformational states, with only one being able to bind its two substrates. The asymmetric binding of ADP to the APS kinase is not only observed in the crystal structure, but can also be detected in solution, using an enzymatic assay. These observations strongly indicate structural changes during the reaction cycle. Furthermore crystals soaked with ADP and APS could be prepared and the corresponding structures could be solved.
  Selected figure(s)  
Figure 1.
Figure 1. Synthesis of PAPS. ATP sulfurylase catalyzes the transfer of sulfate to ATP, releasing pyrophosphate. The intermediate product APS is phosphorylated by APS kinase to yield PAPS.
Figure 3.
Figure 3. Structure of hPAPSS1. Models of the enzyme from different points of view. Monomer A is colored in yellow/red, with a green linker, monomer B is cyan and blue with a pink linker. APS kinase is in yellow and cyan, ATP sulfurylase is in red and blue. ADP is drawn in ball and stick representation, the chloride ions are green. (a) View from the front. (b) View from the side. (c) View from below, along the symmetry axis of the ATP sulfurylase dimer. (d) The domain organization mapped onto the primary sequence. (e) Schematic representation of the 3D domain organization of the hPAPSS1 dimer. The salt bridge is indicated by plus and in circle . The nucleotide binding sites are indicated, red color stands for the molecule of ADP found in the native crystal. The PAPS-loop of the yellow APS kinase domain (monomer A) is not structured, thus the APS binding site has not formed.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2005, 347, 623-635) copyright 2005.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19067028 M.E.Bradley, J.S.Rest, W.H.Li, and N.B.Schwartz (2009).
Sulfate activation enzymes: phylogeny and association with pyrophosphatase.
  J Mol Evol, 68, 1.  
19770499 S.C.Gay, I.H.Segel, and A.J.Fisher (2009).
Structure of the two-domain hexameric APS kinase from Thiobacillus denitrificans: structural basis for the absence of ATP sulfurylase activity.
  Acta Crystallogr D Biol Crystallogr, 65, 1021-1031.
PDB code: 3cr8
  18607083 O.Y.Gavel, A.V.Kladova, S.A.Bursakov, J.M.Dias, S.Texeira, V.L.Shnyrov, J.J.Moura, I.Moura, M.J.Romão, and J.Trincão (2008).
Purification, crystallization and preliminary X-ray diffraction analysis of adenosine triphosphate sulfurylase (ATPS) from the sulfate-reducing bacterium Desulfovibrio desulfuricans ATCC 27774.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 593-595.  
17276460 N.Sekulic, K.Dietrich, I.Paarmann, S.Ort, M.Konrad, and A.Lavie (2007).
Elucidation of the active conformation of the APS-kinase domain of human PAPS synthetase 1.
  J Mol Biol, 367, 488-500.
PDB codes: 2ofw 2ofx
17540769 N.Sekulic, M.Konrad, and A.Lavie (2007).
Structural mechanism for substrate inhibition of the adenosine 5'-phosphosulfate kinase domain of human 3'-phosphoadenosine 5'-phosphosulfate synthetase 1 and its ramifications for enzyme regulation.
  J Biol Chem, 282, 22112-22121.
PDB codes: 2pey 2pez
17010373 J.Chartron, K.S.Carroll, C.Shiau, H.Gao, J.A.Leary, C.R.Bertozzi, and C.D.Stout (2006).
Substrate recognition, protein dynamics, and iron-sulfur cluster in Pseudomonas aeruginosa adenosine 5'-phosphosulfate reductase.
  J Mol Biol, 364, 152-169.
PDB code: 2goy
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 code is shown on the right.