2iux

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[[Image:2iux.gif|left|200px]]
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{{Seed}}
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{{STRUCTURE_2iux| PDB=2iux | SCENE= }}
{{STRUCTURE_2iux| PDB=2iux | SCENE= }}
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'''HUMAN TACE MUTANT G1234'''
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===HUMAN TACE MUTANT G1234===
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 17042482 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17042482}}
==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]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 07:54:59 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 17:36:07 2008''

Revision as of 14:36, 28 July 2008

Image:2iux.png

Template:STRUCTURE 2iux

HUMAN TACE MUTANT G1234

Template:ABSTRACT PUBMED 17042482

About this Structure

2IUX is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structure of testis ACE glycosylation mutants and evidence for conserved domain movement., Watermeyer JM, Sewell BT, Schwager SL, Natesh R, Corradi HR, Acharya KR, Sturrock ED, Biochemistry. 2006 Oct 24;45(42):12654-63. PMID:17042482

Page seeded by OCA on Mon Jul 28 17:36:07 2008

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