title: Structural approaches to probing metal interaction with proteins.
abstract: In this mini-review we focus on metal interactions with proteins with a particular emphasis on the evident synergism between different biophysical approaches toward understanding metallobiology. We highlight three recent examples from our own laboratory. Firstly, we describe metallodrug interactions with glutathione S-transferases, an enzyme family known to attack commonly used anti-cancer drugs. We then describe a protein target for memory enhancing drugs called insulin-regulated aminopeptidase in which zinc plays a role in catalysis and regulation. Finally we describe our studies on a protein, amyloid precursor protein, that appears to play a central role in Alzheimer's disease. Copper ions have been implicated in playing both beneficial and detrimental roles in the disease by binding to different regions of this protein.
authors.affiliation: Biota Structural Biology Laboratory, St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Victoria 3065, Australia.
authors.forename: Lorien J
authors.initials: LJ
authors.lastname: Parker
authors.forename: David B
authors.initials: DB
authors.lastname: Ascher
authors.forename: Chen
authors.initials: C
authors.lastname: Gao
authors.forename: Luke A
authors.initials: LA
authors.lastname: Miles
authors.forename: Hugh H
authors.initials: HH
authors.lastname: Harris
authors.forename: Michael W
authors.initials: MW
authors.lastname: Parker
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D000626:Aminopeptidases / Q000737:chemistry* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D003300:Copper / Q000737:chemistry* / Q000378:metabolism; D005982:Glutathione Transferase / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D013329:Structure-Activity Relationship; D015032:Zinc / Q000737:chemistry* / Q000378:metabolism
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D000970:Antineoplastic Agents; D003300:Copper; D005982:Glutathione Transferase; D000626:Aminopeptidases; D015032:Zinc