208l

From Proteopedia

MUTANT HUMAN LYSOZYME C77A

Structural highlights

208l is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.2Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

LYSC_HUMAN Defects in LYZ are a cause of amyloidosis type 8 (AMYL8) [MIM:105200; also known as systemic non-neuropathic amyloidosis or Ostertag-type amyloidosis. AMYL8 is a hereditary generalized amyloidosis due to deposition of apolipoprotein A1, fibrinogen and lysozyme amyloids. Viscera are particularly affected. There is no involvement of the nervous system. Clinical features include renal amyloidosis resulting in nephrotic syndrome, arterial hypertension, hepatosplenomegaly, cholestasis, petechial skin rash.^[1]

Function

LYSC_HUMAN Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

We previously reported that protein disulfide isomerase (PDI) can dissociate the glutathione molecule in vitro from the mutant human lysozyme (hLZM) C77A-a, which is modified with glutathione at Cys95; however, it seems structurally difficult for PDI to attack either the disulfide bond or the side chain of the cysteine residue of a mixed disulfide. To investigate the function of PDI, we introduced several glutathione and cysteine derivatives at Cys95, instead of the glutathione of C77A-a. Using thiol compounds modified by 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB), we could easily modify the free thiol group of C77A-b (C77A with no glutathionylation), without denaturation. For all of the modifications we tested, a negative correlation was found between the initial rate and the acceleration ratio of the reductive cleavage of mixed disulfides with PDI. A mutant PDI (hPDIM), which has no thiol-disulfide exchange activity, suppressed the reductive cleavage of the mixed disulfide of C77A-a with hPDI, suggesting that hPDI non-covalently interacted with the substrates. Taking account of the results of the structural analysis, we conclude that one of the functions of PDI in vivo lies in relaxing the structure around the disulfide bond, as well as in exchanging the thiol-disulfide bonds.

A role of PDI in the reductive cleavage of mixed disulfides.,Nakamura S, Matsushima M, Song H, Kikuchi M J Biochem. 1996 Sep;120(3):525-30. PMID:8902616^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Pepys MB, Hawkins PN, Booth DR, Vigushin DM, Tennent GA, Soutar AK, Totty N, Nguyen O, Blake CC, Terry CJ, et al.. Human lysozyme gene mutations cause hereditary systemic amyloidosis. Nature. 1993 Apr 8;362(6420):553-7. PMID:8464497 doi:http://dx.doi.org/10.1038/362553a0
↑ Nakamura S, Matsushima M, Song H, Kikuchi M. A role of PDI in the reductive cleavage of mixed disulfides. J Biochem. 1996 Sep;120(3):525-30. PMID:8902616