2c05

File:2c05.gif

spinqualitylabelsall models 2c05, resolution 1.86Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

CRYSTAL STRUCTURES OF EOSINOPHIL-DERIVED NEUROTOXIN IN COMPLEX WITH THE INHIBITORS 5'-ATP, AP3A, AP4A AND AP5A

OverviewOverview

Eosinophil-derived neurotoxin (EDN) is a catalytically proficient member, of the pancreatic ribonuclease superfamily secreted along with other, eosinophil granule proteins during innate host defense responses and, various eosinophil-related inflammatory and allergic diseases. The, ribonucleolytic activity of EDN is central to its antiviral and neurotoxic, activities and possibly to other facets of its biological activity. To, probe the importance of this enzymatic activity further, specific, inhibitors will be of great aid. Derivatives of 5'-ADP are among the most, potent inhibitors currently known. Here, we use X-ray crystallography to, investigate the binding of four natural nucleotides containing this, moiety. 5'-ATP binds in two alternative orientations, one occupying the B2, subsite in a conventional manner and one being a retro orientation with no, ordered adenosine moiety. Diadenosine triphosphate (Ap3A) and diadenosine, tetraphosphate (Ap4A) bind with one adenine positioned at the B2 subsite, the polyphosphate chain extending across the P1 subsite in an ill-defined, conformation, and a disordered second adenosine moiety. Diadenosine, pentaphosphate (Ap5A), the most avid inhibitor of this series, binds in a, completely ordered fashion with one adenine positioned conventionally at, the B2 subsite, the polyphosphate chain occupying the P1 and putative, P(-1) subsites, and the other adenine bound in a retro-like manner at the, edge of the B1 subsite. The binding mode of each of these inhibitors has, features seen in previously determined structures of adenosine, diphosphates. We examine the structure-affinity relationships of these, inhibitors and discuss the implications for the design of improved, inhibitors.

About this StructureAbout this Structure

2C05 is a Single protein structure of sequence from Homo sapiens with B4P and ACY as ligands. Active as Pancreatic ribonuclease, with EC number 3.1.27.5 Structure known Active Site: AC1. Full crystallographic information is available from OCA.

ReferenceReference

Crystal structures of eosinophil-derived neurotoxin (EDN) in complex with the inhibitors 5'-ATP, Ap3A, Ap4A, and Ap5A., Baker MD, Holloway DE, Swaminathan GJ, Acharya KR, Biochemistry. 2006 Jan 17;45(2):416-26. PMID:16401072

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