Document Detail

Ligand-induced structural changes in adenosine 5'-phosphosulfate kinase from Penicillium chrysogenum.
MedLine Citation:
PMID:  12427029     Owner:  NLM     Status:  MEDLINE    
Adenosine 5'-phosphosulfate (APS) kinase catalyzes the second reaction in the two-step, ATP-dependent conversion of inorganic sulfate to 3'-phosphoadenosine 5'-phosphosulfate (PAPS). PAPS serves as the sulfuryl donor for the biosynthesis of all sulfate esters and also as a precursor of reduced sulfur biomolecules in many organisms. Previously, we determined the crystal structure of ligand-free APS kinase from the filamentous fungus, Penicillium chrysogenum [MacRae et al. (2000) Biochemistry 39, 1613-1621]. That structure contained a protease-susceptible disordered region ("mobile lid"; residues 145-170). Addition of MgADP and APS, which together promote the formation of a nonproductive "dead-end" ternary complex, protected the lid from trypsin. This report presents the 1.43 A resolution crystal structure of APS kinase with both ADP and APS bound at the active site and the 2.0 A resolution structure of the enzyme with ADP alone bound. The mobile lid is ordered in both complexes and is shown to provide part of the binding site for APS. That site is formed primarily by the highly conserved Arg 66, Arg 80, and Phe 75 from the protein core and Phe 165 from the mobile lid. The two Phe residues straddle the adenine ring of bound APS. Arg 148, a completely conserved residue, is the only residue in the mobile lid that interacts directly with bound ADP. Ser 34, located in the apex of the P-loop, hydrogen-bonds to the 3'-OH of APS, the phosphoryl transfer target. The structure of the binary E.ADP complex revealed further changes in the active site and N-terminal helix that occur upon the binding/release of (P)APS.
Eric B Lansdon; Irwin H Segel; Andrew J Fisher
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Biochemistry     Volume:  41     ISSN:  0006-2960     ISO Abbreviation:  Biochemistry     Publication Date:  2002 Nov 
Date Detail:
Created Date:  2002-11-12     Completed Date:  2002-12-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  13672-80     Citation Subset:  IM    
Department of Chemistry, University of California, One Shields Avenue, Davis, California 95616, USA.
Data Bank Information
Bank Name/Acc. No.:
PDB/1M7G;  1M7H
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MeSH Terms
Adenosine Diphosphate / chemistry*,  metabolism
Adenosine Phosphosulfate / chemistry*,  metabolism
Crystallography, X-Ray
Models, Molecular
Penicillium chrysogenum / enzymology*
Phosphoadenosine Phosphosulfate / metabolism
Phosphotransferases (Alcohol Group Acceptor) / chemistry*,  metabolism
Protein Conformation
Protein Folding
Reg. No./Substance:
0/Ligands; 482-67-7/Phosphoadenosine Phosphosulfate; 485-84-7/Adenosine Phosphosulfate; 58-64-0/Adenosine Diphosphate; EC 2.7.1.-/Phosphotransferases (Alcohol Group Acceptor); EC kinase

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