2iux: Difference between revisions

Human angiotensin-converting enzyme is an important drug target for which, little structural information has been available until recent years. The, slow progress in obtaining a crystal structure was due to the problem of, surface glycosylation, a difficulty that has thus far been overcome by the, use of a glucosidase-1 inhibitor in the tissue culture medium. However, the prohibitive cost of these inhibitors and incomplete glucosidase, inhibition makes alternative routes to minimizing the N-glycan, heterogeneity desirable. Here, glycosylation in the testis isoform (tACE), has been reduced by Asn-Gln point mutations at N-glycosylation sites, and, the crystal structures of mutants having two and four intact sites have, been solved to 2.0 A and 2.8 A, respectively. Both mutants show close, structural identity with the wild-type. A hinge mechanism is proposed for, substrate entry into the active cleft, based on homology to human ACE2 at, the levels of sequence and flexibility. This is supported by normal-mode, analysis that reveals intrinsic flexibility about the active site of tACE., Subdomain II, containing bound chloride and zinc ions, is found to have, greater stability than subdomain I in the structures of three ACE, homologues. Crystallizable glycosylation mutants open up new possibilities, for cocrystallization studies to aid the design of novel ACE inhibitors.

2IUX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG, ACT, ZN, CL and NXA as [http://en.wikipedia.org/wiki/ligands ligands]. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2IUX OCA].  

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