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Lawrence SH , Jaffe EK
Expanding the concepts in protein structure-function relationships and enzyme kinetics: Teaching using morpheeins
Biochemistry and Molecular Biology Education. 2008 Jul-Aug;36(4) :274-283
PMID: ISI:000258256600005   
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Abstract
A morpheein is a homo-oligomeric protein that can exist as an ensemble of physiologically significant and functionally distinct alternate quaternary assemblies. Morpheeins exist in nature and use conformational equilibria between different tertiary structures to form distinct oligomers as a means of regulating their function. Notably, alternate morpheein forms are not misfolded forms of a protein; they are differently assembled native states that contain alternate subunit conformations. Transitions between alternate morpheein assemblies involve oligomer dissociation, conformational change in the dissociated state, and reassembly to a different oligomer. These transitions occur in response to the protein's environment, for example, effector molecules, and represent a new model of allosteric regulation. The unique features of morpheeins are being revealed through detailed characterization of the prototype enzyme, porphobilinogen synthase, which exists in a dynamic equilibrium of a high activity octamer, a low activity hexamer, and two dimer conformations. Morpheeins are likely far more common than previously appreciated. There are, however, both intellectual and experimental barriers to recognizing proteins as morpheeins. These barriers derive from the way we were taught and continue to teach about protein folding, protein purification, protein structure-function relationships, and enzyme kinetics. This article explores some of these limitations and encourages incorporation of morpheeins into both introductory and advanced biochemistry classes.
Notes
ISI Document Delivery No.: 334YB Times Cited: 0 Cited Reference Count: 34 Cited References: ANFINSEN CB, 1973, SCIENCE, V181, P223 ARMONOMER A, 2008, J MOL BIOL, V376, P971 BAEYENS KJ, 1999, ACTA CRYSTALLOGR D 4, V55, P772 BREINIG S, 2003, NAT STRUCT BIOL, V10, P757 CASPAR DLD, 1962, COLD SPRING HARB SYM, V27, P1 DAWSON JP, 2005, MOL CELL BIOL, V25, P7734 DUNKER AK, 2001, NAT BIOTECHNOL, V19, P805 FRIEDEN C, 1970, J BIOL CHEM, V245, P5788 HAYOUKA Z, 2007, P NATL ACAD SCI USA, V104, P8316 HAYOUKA Z, 2008, BIOPOLYMERS IN PRESS HE MM, 2005, SCIENCE, V310, P1022 JAFFE EK, 1987, BIOCHEMISTRY-US, V26, P4258 JAFFE EK, 2005, TRENDS BIOCHEM SCI, V30, P490 JAMES LC, 2003, TRENDS BIOCHEM SCI, V28, P361 JOHNSON JE, 1996, P NATL ACAD SCI USA, V93, P27 KERVINEN J, 2000, BIOCHEMISTRY-US, V39, P9018 KIMCHISARFATY C, 2007, SCIENCE, V315, P525 KOSHLAND DE, 1966, BIOCHEMISTRY-US, V5, P365 LAWRENCE SH, 2008, CHEMBIOL IN PRESS LEYVA JA, 2003, MOL MEMBR BIOL, V20, P27 LIU Y, 2002, PROTEIN SCI, V11, P1285 LU HP, 2004, CURR PHARM BIOTECHNO, V5, P261 MILLSDAVIES NL, 2000, THESIS U SOUTHAMPTON MONOD J, 1965, J MOL BIOL, V12, P88 NICKERSON K, 1969, CURR MOD BIOL, V2, P303 NICKERSON KW, 1973, J THEOR BIOL, V40, P507 SCHNELL JR, 2004, ANNU REV BIOPH BIOM, V33, P119 SCOPES RK, 1993, PROTEIN PURIFICATION, P408 SEGEL IH, 1993, ENZYME KINETICS BEHA, P957 SELWOOD T, 2008, BIOCHEMISTRY-US, V47, P3245 STEWART L, 1999, FEBS LETT, V454, P229 TANG L, 2005, J BIOL CHEM, V280, P15786 TANG L, 2006, J BIOL CHEM, V281, P6682 TSOU CL, 1998, BIOCHEMISTRY-MOSCOW+, V63, P253 Lawrence, Sarah H. Jaffe, Eileen K. JOHN WILEY & SONS INC; 111 RIVER ST, HOBOKEN, NJ 07030 USA