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Michael C. Wiener
University of Virginia
61Publications
23H-index
2,150Citations
Publications 58
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#1Brandon R. Goblirsch (UVA: University of Virginia)H-Index: 7
#2Edward E. Pryor (UVA: University of Virginia)H-Index: 3
Last.Michael C. Wiener (UVA: University of Virginia)H-Index: 23
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#2Buenafe T. AracheaH-Index: 2
Last.Michael C. WienerH-Index: 23
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#1Brandon R. Goblirsch (UVA: University of Virginia)H-Index: 7
#2Buenafe T. Arachea (UVA: University of Virginia)H-Index: 2
Last.Michael C. Wiener (UVA: University of Virginia)H-Index: 23
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The integral membrane protein zinc metalloprotease ZMPSTE24 possesses a completely novel structure, comprising seven long kinked transmembrane helices that encircle a voluminous 14 000 A3 cavity within the membrane. Functionally conserved soluble zinc metalloprotease residues are contained within this cavity. As part of an effort to understand the structural and functional relationships between ZMPSTE24 and soluble zinc metalloproteases, the inhibition of ZMPSTE24 by phosphoramidon [N-(α-rhamnop...
1 CitationsSource
#1Buenafe T. Arachea (UVA: University of Virginia)H-Index: 2
#2Michael C. Wiener (UVA: University of Virginia)H-Index: 23
The Intramolecular Quenched Fluorescence (IQF) protease assay utilizes peptide substrates containing donor-quencher pairs that flank the scissile bond. Following protease cleavage, the dequenched donor emission of the product is subsequently measured. Inspection of the IQF literature indicates that rigorous treatment of systematic errors in observed fluorescence arising from inner-filter absorbance (IF) and non-specific intermolecular quenching (NSQ) is incompletely performed. As substrate and p...
4 CitationsSource
#1Emily R. Hildebrandt (UGA: University of Georgia)H-Index: 8
#2Buenafe T. Arachea (UVA: University of Virginia)H-Index: 2
Last.Walter K. Schmidt (UGA: University of Georgia)H-Index: 5
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Abstract Rce1p and Ste24p are integral membrane proteins involved in the proteolytic maturation of isoprenylated proteins. Extensive published evidence indicates that Rce1p requires the isoprenyl moiety as an important substrate determinant. By contrast, we report that Ste24p can cleave both isoprenylated and non-prenylated substrates in vitro, indicating that the isoprenyl moiety is not required for substrate recognition. Steady-state enzyme kinetics are significantly different for prenylated v...
9 CitationsSource
#1Michael C. Wiener (UVA: University of Virginia)H-Index: 23
The first integral membrane protein X-ray crystal structure was solved in 1985 (Deisenhofer et al., 1985 ▸). Thirty years later, they remain a frontier of structural biology, and an area of intense fundamental and practical interest. The structural and functional bases of many critical biological processes that occur in and across membranes remain largely unknown. And, on the practical side, membrane proteins are considered to be the target of many, if not most, current and future drugs (Yildiri...
1 CitationsSource
#1Edward E. Pryor (UVA: University of Virginia)H-Index: 3
#2Michael C. Wiener (UVA: University of Virginia)H-Index: 23
Intrinsically disordered regions in proteins possess important biological roles including transcriptional regulation, molecular recognition, and provision of sites for posttranslational modification. In three-dimensional crystallization of both soluble and membrane proteins, identification and removal of disordered regions is often necessary for obtaining crystals possessing sufficient long-range order for structure determination. Disordered regions can be identified experimentally, with techniq...
9 CitationsSource
#1Edward E. Pryor (UVA: University of Virginia)H-Index: 3
#2P. Horanyi (UVA: University of Virginia)H-Index: 10
Last.Mark E. Dumont (UR: University of Rochester)H-Index: 27
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Posttranslational lipidation provides critical modulation of the functions of some proteins. Isoprenoids (i.e., farnesyl or geranylgeranyl groups) are attached to cysteine residues in proteins containing C-terminal CAAX sequence motifs (where A is an aliphatic residue and X is any residue). Isoprenylation is followed by cleavage of the AAX amino acid residues and, in some cases, by additional proteolytic cuts. We determined the crystal structure of the CAAX protease Ste24p, a zinc metalloproteas...
51 CitationsSource
#1Edward E. PryorH-Index: 3
#2P. HoranyiH-Index: 10
Last.Michael C. WienerH-Index: 23
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#1Ursula Pieper (UCSF: University of California, San Francisco)H-Index: 30
#2Avner Schlessinger (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 29
Last.Andrej Sali (UCSF: University of California, San Francisco)H-Index: 97
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Given the recent successes in determining membrane-protein structures, we explore the tractability of determining representatives for the entire human membrane proteome. This proteome contains 2,925 unique integral α-helical transmembrane-domain sequences that cluster into 1,201 families sharing more than 25% sequence identity. Structures of 100 optimally selected targets would increase the fraction of modelable human α-helical transmembrane domains from 26% to 58%, providing structure and funct...
49 CitationsSource
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