2IUL

Human tACE g13 mutant

Summary for 2IUL

• Entry DOI: 10.2210/pdb2iul/pdb
• Related: 1O86 1O8A 1UZE 1UZF 2IUX
• Descriptor: ANGIOTENSIN-CONVERTING ENZYME, beta-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: hydrolase, phosphorylation, carboxypeptidase, metal-binding, transmembrane, metalloprotease, peptidyl dipeptidase, alternative splicing, type-i membrane-anchored protein, glycosidase, polymorphism, glycoprotein, ac, zinc, mutant, membrane, chloride, protease
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 69723.73

Authors

Watermeyer, J.M.,Sewell, B.T.,Natesh, R.,Corradi, H.R.,Acharya, K.R.,Sturrock, E.D. (deposition date: 2006-06-06, release date: 2006-10-25, Last modification date: 2023-12-13)

Primary citation

Watermeyer, J.M.,Sewell, B.T.,Schwager, S.L.,Natesh, R.,Corradi, H.R.,Acharya, K.R.,Sturrock, E.D.
Structure of Testis Ace Glycosylation Mutants and Evidence for Conserved Domain Movement.
Biochemistry, 45:12654-, 2006

PubMed Abstract: 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.

PubMed: 17042482
DOI: 10.1021/BI061146Z

Experimental method

X-RAY DIFFRACTION (2.01 Å)