1KYI

HslUV (H. influenzae)-NLVS Vinyl Sulfone Inhibitor Complex

Summary for 1KYI

• Entry DOI: 10.2210/pdb1kyi/pdb
• Related: 1G3I 1G3K 1G41 1JJW
• Descriptor: ATP-dependent hsl protease ATP-binding subunit hslU, ATP-dependent protease hslV, ADENOSINE-5'-TRIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: prokaryotic proteasome, protease, aaa-protein, atp-dependent chaperone; clp/hsp100, vinyl sulfone inhibitor, chaperone-hydrolase complex, chaperone/hydrolase
• Biological source: Haemophilus influenzae; More
• Cellular location: Cytoplasm (By similarity): P43773 P43772
• Total number of polymer chains: 24
• Total formula weight: 834898.39

Authors

Sousa, M.C.,Kessler, B.M.,Overkleeft, H.S.,McKay, D.B. (deposition date: 2002-02-04, release date: 2002-05-15, Last modification date: 2024-10-30)

Primary citation

Sousa, M.C.,Kessler, B.M.,Overkleeft, H.S.,McKay, D.B.
Crystal Structure of HslUV Complexed with a Vinyl Sulfone Inhibitor: Corroboration of a Proposed Mechanism of Allosteric Activation of HslV by HslU
J.Mol.Biol., 318:779-785, 2002

PubMed Abstract: On the basis of the structure of a HslUV complex, a mechanism of allosteric activation of the HslV protease, wherein binding of the HslU chaperone propagates a conformational change to the active site cleft of the protease, has been proposed. Here, the 3.1 A X-ray crystallographic structure of Haemophilus influenzae HslUV complexed with a vinyl sulfone inhibitor is described. The inhibitor, which reacts to form a covalent linkage to Thr1 of HslV, binds in an "antiparallel beta" manner, with hydrogen-bond interactions between the peptide backbone of the protease and that of the inhibitor, and with two leucinyl side chains of the inhibitor binding in the S1 and S3 specificity pockets of the protease. Comparison of the structure of the HslUV-inhibitor complex with that of HslV without inhibitor and in the absence of HslU reveals that backbone interactions would correctly position a substrate for cleavage in the HslUV complex, but not in the HslV protease alone, corroborating the proposed mechanism of allosteric activation. This activation mechanism differs from that of the eukaryotic proteasome, for which binding of activators opens a gated channel that controls access of substrates to the protease, but does not perturb the active site environment.

PubMed: 12054822
DOI: 10.1016/S0022-2836(02)00145-6

Experimental method

X-RAY DIFFRACTION (3.1 Å)