Sandbox chaperones: Difference between revisions

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The inactive form of Hsp90 is open, but binding of ATP causes the molecule to close into the active form. The N-terminal domain is the cite of the ATP binding pocket. Amino acids Leu34, Asn37, Asp79, Asn92, Lys98, Gly121, and Phe124 are in the N-terminal domain and are directly involved in ATP binding. Mg2+ is also present and involved in electrostatic bonding interactions with ATP. This results in a high-affinity ATP-binding site. Hsp90 binds ATP when in the open, inactive conformation and then cleaves the ATP into ADP to drive the conformational change into the closed, active form.<ref>Prodromou C, Roe SM, O'Brien R, Ladbury JE, Piper PW, Pearl LH (July 1997). "Identification and structural characterization of the ATP/ADP-binding site in the Hsp90 molecular chaperone". Cell 90 (1): 65–75. doi:10.1016/S0092-8674(00)80314-1. PMID 9230303.</ref>

The protein binding domain is in the C-terminus. Hydrophobic residues in the C-terminus are exposed while the dimer is in the open conformation, allowing unfolded and misfolded client proteins to bind. When the N-terminal domain hydrolyzes ATP and drives a confirmation change the C-terminal domain clamps down in the client protein.<ref>PMID 9295332.</ref>

The protein binding domain is in the C-terminus. Hydrophobic residues in the C-terminus are exposed while the dimer is in the open conformation, allowing unfolded and misfolded client proteins to bind. When the N-terminal domain hydrolyzes ATP and drives a confirmation change the C-terminal domain clamps down in the client protein.<ref>renert JP, Sullivan WP, Fadden P, Haystead TA, Clark J, Mimnaugh E, Krutzsch H, Ochel HJ, Schulte TW, Sausville E, Neckers LM, Toft DO (September 1997). "The amino-terminal domain of heat shock protein 90 (hsp90) that binds geldanamycin is an ATP/ADP switch domain that regulates hsp90 conformation". J. Biol. Chem. 272 (38): 23843–50. doi:10.1074/jbc.272.38.23843. PMID 9295332.</ref>

== Disease ==

Sandbox chaperones: Difference between revisions

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 The inactive form of Hsp90 is open, but binding of ATP causes the molecule to close into the active form. The N-terminal domain is the cite of the ATP binding pocket. Amino acids Leu34, Asn37, Asp79, Asn92, Lys98, Gly121, and Phe124 are in the N-terminal domain and are directly involved in ATP binding. Mg2+ is also present and involved in electrostatic bonding interactions with ATP. This results in a high-affinity ATP-binding site. Hsp90 binds ATP when in the open, inactive conformation and then cleaves the ATP into ADP to drive the conformational change into the closed, active form.<ref>Prodromou C, Roe SM, O'Brien R, Ladbury JE, Piper PW, Pearl LH (July 1997). "Identification and structural characterization of the ATP/ADP-binding site in the Hsp90 molecular chaperone". Cell 90 (1): 65–75. doi:10.1016/S0092-8674(00)80314-1. PMID 9230303.</ref>
-The protein binding domain is in the C-terminus. Hydrophobic residues in the C-terminus are exposed while the dimer is in the open conformation, allowing unfolded and misfolded client proteins to bind. When the N-terminal domain hydrolyzes ATP and drives a confirmation change the C-terminal domain clamps down in the client protein.<ref>PMID 9295332.</ref>
+The protein binding domain is in the C-terminus. Hydrophobic residues in the C-terminus are exposed while the dimer is in the open conformation, allowing unfolded and misfolded client proteins to bind. When the N-terminal domain hydrolyzes ATP and drives a confirmation change the C-terminal domain clamps down in the client protein.<ref>renert JP, Sullivan WP, Fadden P, Haystead TA, Clark J, Mimnaugh E, Krutzsch H, Ochel HJ, Schulte TW, Sausville E, Neckers LM, Toft DO (September 1997). "The amino-terminal domain of heat shock protein 90 (hsp90) that binds geldanamycin is an ATP/ADP switch domain that regulates hsp90 conformation". J. Biol. Chem. 272 (38): 23843–50. doi:10.1074/jbc.272.38.23843. PMID 9295332.</ref>
 == Disease ==