Evaluation of the Functional Role of the Heme-6-propionate Side Chain in Cytochrome P450cam

2008 ◽  
Vol 130 (2) ◽  
pp. 432-433 ◽  
Author(s):  
Katsuyoshi Harada ◽  
Keisuke Sakurai ◽  
Kenichiro Ikemura ◽  
Takashi Ogura ◽  
Shun Hirota ◽  
...  
Keyword(s):  
Functional Role ◽  
Side Chain ◽  
Cytochrome P450cam

scholarly journals Structural and Functional Role of the Extracellular S5-P Linker in the HERG Potassium Channel

2002 ◽  
Vol 120 (5) ◽  
pp. 723-737 ◽  
Author(s):  
Jie Liu ◽  
Mei Zhang ◽  
Min Jiang ◽  
Gea-Ny Tseng
Keyword(s):  
Functional Role ◽  
Function Analysis ◽  
Voltage Sensor ◽  
Herg Channel ◽  
Side Chain ◽  
Voltage Sensitivity ◽  
Fast Kinetics ◽  
Channel Function ◽  
Outer Vestibule

C-type inactivation in the HERG channel is unique among voltage-gated K channels in having extremely fast kinetics and strong voltage sensitivity. This suggests that HERG may have a unique outer mouth structure (where conformational changes underlie C-type inactivation), and/or a unique communication between the outer mouth and the voltage sensor. We use cysteine-scanning mutagenesis and thiol-modifying reagents to probe the structural and functional role of the S5-P (residues 571–613) and P-S6 (residues 631–638) linkers of HERG that line the outer vestibule of the channel. Disulfide formation involving introduced cysteine side chains or modification of side chain properties at “high-impact” positions produces a common mutant phenotype: disruption of C-type inactivation, reduction of K+ selectivity, and hyperpolarizing shift in the voltage-dependence of activation. In particular, we identify 15 consecutive positions in the middle of the S5-P linker (583–597) where side chain modification has marked impact on channel function. Analysis of the degrees of mutation-induced perturbation in channel function along 583–597 reveals an α-helical periodicity. Furthermore, the effects of MTS modification suggest that the NH2-terminal of this segment (position 584) may be very close to the pore entrance. We propose a structural model for the outer vestibule of the HERG channel, in which the 583–597 segment forms an α-helix. With the NH2 terminus of this helix sitting at the edge of the pore entrance, the length of the helix (∼20 Å) allows its other end to reach and interact with the voltage-sensing domain. Therefore, the “583–597 helix” in the S5-P linker of the HERG channel serves as a bridge of communication between the outer mouth and the voltage sensor, that may make important contribution to the unique C-type inactivation phenotype.

Structure and Ligand Binding Properties of Myoglobins Reconstituted with Monodepropionated Heme:  Functional Role of Each Heme Propionate Side Chain†,‡

Biochemistry ◽  
2007 ◽  
Vol 46 (33) ◽  
pp. 9406-9416 ◽  
Author(s):  
Katsuyoshi Harada ◽  
Masatomo Makino ◽  
Hiroshi Sugimoto ◽  
Shun Hirota ◽  
Takashi Matsuo ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Functional Role ◽  
Side Chain ◽  
Binding Properties

Expression and functional role of c-Kit and erbB2 in human hepatoblastoma.

2009 ◽  
Vol 221 (03) ◽  
Author(s):  
B Steiger ◽  
I Leuschner ◽  
D Denkhaus ◽  
D von Schweinitz ◽  
T Pietsch
Keyword(s):  
Functional Role
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