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Catalytic Site Atlas Version 2.2.12
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CSA entry for 1hpm
Original Entry
Title:
Hydrolase (acting on acid anhydrides)
Compound:
44k atpase fragment (n-terminal) of 7okda heat-shock cognate protein (e.c.3.6.1.3
Mutant:
No
UniProt/Swiss-Prot:
P19120-HS7C_BOVIN
EC Class:
3.6.1.3
Other CSA Entries:
Overview of all sites for 1hpm
Homologues of 1hpm
Entries for UniProt/Swiss-Prot: P19120
Entries for EC: 3.6.1.3
Other Databases:
PDB entry: 1hpm
PDBsum entry: 1hpm
UniProt/Swiss-Prot: P19120
IntEnz entry: 3.6.1.3
Literature Report:
Introduction:
Hsc70 is a molecular chaperone of the 70 kilodalton heat shock protein family. It is thought to facilitate protein folding by binding to nascent or misfolding segments of peptide, thus preventing their aggregation. The peptide binding activity is regulated by ATP binding and hydrolysis: with ADP bound Hsc70 binds peptides tightly, but when ATP binds it releases them. The ATPase domain of Hsc70 is located at the N-terminus of the protein and can be isolated as an independent, fully functional entity by proteolysis of the complete protein or as a recombinant expression product.
Mechanism:
Hsc70 catalyses ATP hydrolysis by using K+ and Mg2+ to stabilise negative charge in the transition state of phosphoryl transfer. One K+ ion (in site 1, K 490 in structure 1hpm) interacts with the beta phosphate while a second (in site 2, K 491 in structure 1hpm) interacts with the gamma phosphate. Lys 71 is proposed to stabilise a hydroxide ion or water molecule for nucleophilic attack on the gamma phosphate.
Sites:

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Found by:
Literature reference 
PsiBLAST alignment on 1kaz

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
487 0
ElectrostaticTransition state
Proposed to stabilise negative charge in the transition state.
Evidence from paper Evidence concerns Evidence type
PubMed ID 7836458 Current protein Residue is positioned appropriately (ligand position known)

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
490 0
ElectrostaticTransition state
Interacts with the beta phosphate; proposed to stabilise negative charge in the transition state.
Evidence from paper Evidence concerns Evidence type
PubMed ID 9585559 Current protein Ligand is essential for catalysis
PubMed ID 7836458 Current protein Residue is positioned appropriately (ligand position known)

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
491 0
ElectrostaticTransition state
Interacts with the gamma phosphate of ATP; proposed to stabilise negative charge in the transition state.
Evidence from paper Evidence concerns Evidence type
PubMed ID 9585559 Current protein Ligand is essential for catalysis
PubMed ID 7836458 Current protein Residue is positioned appropriately (ligand position known)

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
LYSA 71 71Sidechain
ElectrostaticWater
Proposed to stabilise a hydroxide ion or water molecule for nucleophilic attack on the gamma phosphate of ATP.
Evidence from paper Evidence concerns Evidence type
PubMed ID 8663302 Current protein Residue is positioned appropriately (ligand position known)
PubMed ID 8663302 Current protein Mutagenesis of residue
References:
1
How potassium affects the activity of the molecular chaperone Hsc70. II. Potassium binds specifically in the ATPase active site.
S. M. Wilbanks and D. B. McKay
J Biol Chem 270, (5) 2251-7, (1995).
7836458
2
Structural replacement of active site monovalent cations by the epsilon-amino group of lysine in the ATPase fragment of bovine Hsc70.
S. M. Wilbanks and D. B. McKay
Biochemistry 37, (20) 7456-62, (1998).
9585559
3
Lysine 71 of the chaperone protein Hsc70 Is essential for ATP hydrolysis.
M. C. O'Brien and K. M. Flaherty and D. B. McKay
J Biol Chem 271, (27) 15874-8, (1996).
8663302
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