The crystal structure of Pichia pastoris lysyl oxidase

被引:88
作者
Duff, AP
Cohen, AE
Ellis, PJ
Kuchar, JA
Langley, DB
Shepard, EM
Dooley, DM [1 ]
Freeman, HC
Guss, JM
机构
[1] Univ Sydney, Sch Mol & Microbial Biosci, Sydney, NSW 2006, Australia
[2] Stanford Synchrotron Radiat Lab, Menlo Pk, CA 94025 USA
[3] Montana State Univ, Dept Chem & Biochem, Bozeman, MT 59717 USA
关键词
D O I
10.1021/bi035338v
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Pichia pastoris lysyl oxidase (PPLO) is unique among the structurally characterized copper amine oxidases in being able to oxidize the side chain of lysine residues in polypeptides. Remarkably, the yeast PPLO is nearly as effective in oxidizing a mammalian tropoelastin substrate as is a true mammalian lysyl oxidase isolated from bovine aorta. Thus, PPLO is functionally related to the copper-containing lysyl oxidases despite the lack of any significant sequence similarity with these enzymes. The structure of PPLO has been determined at 1.65 Angstrom resolution. PPLO is a homodimer in which each subunit contains a Type II copper atom and a topaquinone cofactor (TPQ) formed by the posttranslational modification of a tyrosine residue. While PPLO has tertiary and quaternary topologies similar to those found in other quinone-containing copper amine oxidases, its active site is substantially more exposed and accessible. The structural elements that are responsible for the accessibility of the active site are identified and discussed.
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收藏
页码:15148 / 15157
页数:10
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