1lmt

From Proteopedia

STRUCTURE OF A CONFORMATIONALLY CONSTRAINED ARG-GLY-ASP SEQUENCE INSERTED INTO HUMAN LYSOZYME

Structural highlights

1lmt 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 1.6Å
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

To examine the effect of a conformational constraint introduced into the Arg-Gly-Asp (RGD) sequence on cell adhesion activity, we constructed a mutant protein by inserting an RGD-containing sequence flanked by two Cys residues between Val74 and Asn75 of human lysozyme. The CRGDSC-inserted lysozyme was expressed in yeast, purified, and designated as Cys-RGD4. Using baby hamster kidney cells, Cys-RGD4 was shown to possess even higher cell adhesion activity than that of the RGDS-inserted lysozyme, RGD4. The Cys-RGD4 protein was co-crystallized with a lysozyme inhibitor, tri-N-acetylchitotriose, and the three-dimensional structure was determined at 1.6-A resolution by x-ray crystallography. In contrast to RGD4, the inserted RGD-containing region of Cys-RGD4 was well defined. The structural analysis revealed that the two inserted Cys residues form a new disulfide bond in Cys-RGD4, as expected, and that the RGD region assumes a type II' beta-turn conformation of Gly-Asp with a hydrogen bond between the C = O of Arg and the H-N of Ser. In addition, it was confirmed that two more hydrogen bonds are present in the RGD region of the Cys-RGD4 lysozyme. These results suggest that the conformation of the RGD-containing region is rigid and stable in the Cys-RGD4 molecule and that the type II' beta-turn structure of RGD is essential for binding to integrins with high affinity.

Structure of a conformationally constrained Arg-Gly-Asp sequence inserted into human lysozyme.,Yamada T, Song H, Inaka K, Shimada Y, Kikuchi M, Matsushima M J Biol Chem. 1995 Mar 17;270(11):5687-90. PMID:7890692^[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
↑ Yamada T, Song H, Inaka K, Shimada Y, Kikuchi M, Matsushima M. Structure of a conformationally constrained Arg-Gly-Asp sequence inserted into human lysozyme. J Biol Chem. 1995 Mar 17;270(11):5687-90. PMID:7890692