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| {{STRUCTURE_2iul| PDB=2iul | SCENE= }} | | {{STRUCTURE_2iul| PDB=2iul | SCENE= }} |
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| '''HUMAN TACE G13 MUTANT'''
| | ===HUMAN TACE G13 MUTANT=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_17042482}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 17042482 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_17042482}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Type-i membrane-anchored protein]] | | [[Category: Type-i membrane-anchored protein]] |
| [[Category: Zinc]] | | [[Category: Zinc]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 07:54:07 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 21:46:49 2008'' |