biochem 10
Post on 03-Jun-2018
218 Views
Preview:
TRANSCRIPT
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 1/79
Biochemistry 2/e - Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
Chapter 10
Membrane Transportto accompany
Biochemistry, 2/e
byReginald Garrett and Charles Grisham
All rights reserved. Requests for permission to make copies of any part of the work
should be mailed to: Permissions Department, Harcourt Brace & Company, 6277Sea Harbor Drive, Orlando, Florida 32887-6777
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 2/79
Biochemistry 2/e - Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
Outline
• 10.1 Passive Diffusion
• 10.2 Facilitated Diffusion
• 10.3 Active Transport
• 10.4 - 10.6 Transport Driven by ATP, light, etc.
• 10.7 Group Translocation
• 10.8 Specialized Membrane Pores
• 10.9 Ionophore Antibiotics
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 3/79
Biochemistry 2/e - Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
Passive Diffusion
No special proteins needed
• Transported species simply moves
down its concentration gradient - fromhigh [c] to low [c]
• Be able to use Eq. 10.1 and 10.2
•
High permeability coefficients usuallymean that passive diffusion is not the
whole story
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 4/79
Biochemistry 2/e - Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 5/79
Biochemistry 2/e - Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 6/79
Biochemistry 2/e - Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
Facilitated Diffusion
G negative, but proteins assist
• Solutes only move in the
thermodynamically favored direction
• But proteins may "facilitate" transport,increasing the rates of transport
• Understand plots in Figure 10.3
• Two important distinguising features: – solute flows only in the favored direction
– transport displays saturation kinetics
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 7/79
Biochemistry 2/e - Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 8/79
Biochemistry 2/e - Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 9/79
Biochemistry 2/e - Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 10/79
Biochemistry 2/e - Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 11/79
Biochemistry 2/e - Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 12/79
Biochemistry 2/e - Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
Active Transport Systems
Energy input drives transport
• Some transport must occur such that
solutes flow against thermodynamic
potential• Energy input drives transport
• Energy source and transport machinery
are "coupled" • Energy source may be ATP, light or a
concentration gradient
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 13/79
Biochemistry 2/e - Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
The Sodium Pump
aka Na,K-ATPase
• Large protein - 120 kD and 35 kD subunits
• Maintains intracellular Na low and K high• Crucial for all organs, but especially for
neural tissue and the brain
• ATP hydrolysis drives Na out and K in
• Alpha subunit has ten transmembrane
helices with large cytoplasmic domain
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 14/79
Biochemistry 2/e - Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 15/79
Biochemistry 2/e - Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 16/79
Biochemistry 2/e - Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
Na,K Transport
• ATP hydrolysis occurs via an E-P
intermediate
• Mechanism involves two enzymeconformations known as E1 and E2
• Cardiac glycosides inhibit by binding to
outside
/ G & G
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 17/79
Biochemistry 2/e - Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
Bi h i t 2/ G tt & G i h
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 18/79
Biochemistry 2/e - Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
Bi h i t 2/ G tt & G i h
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 19/79
Biochemistry 2/e - Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
Bi h i t 2/ G tt & G i h
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 20/79
Biochemistry 2/e - Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
Na,K Transport
• Hypertension involves apparent
inhibition of sodium pump. Inhibition in
cells lining blood• Vessel walls results in Na,Ca
accumulation
• Studies show this inhibitor to beouabain!
Bi h i t 2/ G tt & G i h
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 21/79
Biochemistry 2/e - Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
Calcium Transport in Muscle
A process akin to Na,K transport
• Calcium levels in resting muscle cytoplasm are
maintained low by Ca-ATPase - a Ca pump• Calcium is pumped into the sarcoplasmic
reticulum (SR) by a 110 kD protein that is very
similar to the alpha subunit of Na,K-ATPase
• Aspartyl phosphate E-P intermediate is at Asp-
351 and Ca-pump also fits the E1-E2 model
Bi h i t 2/ G tt & G i h
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 22/79
Biochemistry 2/e - Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
Bi h i t 2/ G tt & G i h
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 23/79
Biochemistry 2/e - Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
Biochemistr 2/e Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 24/79
Biochemistry 2/e - Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 25/79
Biochemistry 2/e Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 26/79
Biochemistry 2/e - Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
Biochemistry 2/e Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 27/79
Biochemistry 2/e - Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
The Gastric H,K-ATPase
• This is the largest concentration
gradient across a membrane in
eukaryotic organisms!• H,K-ATPase is similar in many respects
to Na,K-ATPase and Ca-ATPase
Biochemistry 2/e Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 28/79
Biochemistry 2/e - Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
Osteoclast Proton PumpsHow your body takes your bones apart!
• Bone material undergoes ongoing remodeling
– osteoclasts tear down bone tissue•
– osteoblasts build it back up
• Osteoclasts function by secreting acid into
the space between the osteoclast membrane
and the bone surface - acid dissolves the Ca-
phosphate matrix of the bone• An ATP-driven proton pump in the membrane
does this!
Biochemistry 2/e Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 29/79
Biochemistry 2/e - Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
Biochemistry 2/e Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 30/79
Biochemistry 2/e - Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
The MDR ATPase
aka the P-glycoprotein
• Animal cells have a transport system
that is designed to recognize foreignorganic molecules
• This organic molecule pump recognizes
a broad variety of molecules andtransports them out of the cell using the
hydrolytic energy of ATP
Biochemistry 2/e Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 31/79
Biochemistry 2/e - Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 32/79
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 33/79
Biochemistry 2/e - Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 34/79
Biochemistry 2/e - Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
Light-Driven H + Transport
The Bacteriorhodopsin story • Halobacterium halobium, the salt-loving
bacterium, carries out normal respiration if
O2 and substrates are plentiful
• But when substrates are lacking, it can
survive by using bacteriorhodopsin and
halorhodopsin to capture light energy
• Purple patches of H. halobium are 75% bRand 25% lipid - a "2D crystal" of bR - ideal
for structural studies
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 35/79
Biochemistry 2/e Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 36/79
Biochemistry 2/e Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 37/79
Biochemistry 2/e Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 38/79
Biochemistry 2/e Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
Bacteriorhodopsin
Protein opsin and retinal chromophore
• Retinal is bound to opsin via a Schiff
base link
• The Schiff base (at Lys-216) can be
protonated, and this site is one of the
sites that participate in H+ transport
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 39/79
Biochemistry 2/e Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 40/79
Biochemistry 2/e Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
Bacteriorhodopsin
• Lys-216 is buried in the middle of the 7-
TMS structure of bR, and retinal lies
mostly parallel to the membrane andbetween the helices
• Light absorption converts all-trans
retinal to 13-cis configuration - seeFigure 10.22
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 41/79
Biochemistry 2/e Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
Bacteriorhodopsin
The protons visit the aspartates....
• Asp-85 and Asp-96 lie on opposite
sides of a membrane-spanning helix
• These remarkable aspartates have pKa
values around 11! (Why?)
•
Protons are driven from Asp-96 to theSchiff base at Lys-216 to Asp-85 and
out of the cell
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 42/79
Biochemistry 2/e Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
Halorhodopsin
• Halorhodopsin transports Cl - instead of H +
• Halorhodopsin has Lys-242 Schiff base but
no aspartates and no deprotonation ofSchiff base during the transport cycle
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 43/79
y &
Copyright © 1999 by Harcourt Brace & Company
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 44/79
y
Copyright © 1999 by Harcourt Brace & Company
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 45/79
y
Copyright © 1999 by Harcourt Brace & Company
Secondary Active Transport
Transport processes driven by ion
gradients
• Many amino acids and sugars areaccumulated by cells in transport
processes driven by ion gradients
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 46/79
y
Copyright © 1999 by Harcourt Brace & Company
Secondary Active Transport
• Symport - ion and the amino acid or
sugar are transported in the same
direction across the membrane
• Antiport - ion and transported species
move in opposite directions
•
Several examples are described inTable 10.2
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 47/79
y
Copyright © 1999 by Harcourt Brace & Company
Group Translocation
The phosphotransferase system (PTS)
• Discovered by Saul Roseman in 1964
• Sugars are phosphorylated from PEP
during transport into E. coli cells
• Four proteins required: EI, HPr, EII, and
EIII
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 48/79
y
Copyright © 1999 by Harcourt Brace & Company
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 49/79
y
Copyright © 1999 by Harcourt Brace & Company
Group Translocation
• EI and HPr are universal and work for
all sugars
• EII and EIII are specific for each sugar• Mechanism involves transfer of P from
PEP to EI and then to HPr and then to 2
sites on EIII and then finallyphosphorylation of sugar
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 50/79
Copyright © 1999 by Harcourt Brace & Company
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 51/79
Copyright © 1999 by Harcourt Brace & Company
Porins
Found both in Gram-negative bacteria and inmitochondrial outer membrane
• Porins are pore-forming proteins - 30-50 kD
• General or specific - exclusion limits 600-6000• Most arrange in membrane as trimers
• High homology between various porins
• Porin from Rhodobacter capsulatus has 16-stranded beta barrel that traverses the
membrane to form the pore (with eyelet!)
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 52/79
Copyright © 1999 by Harcourt Brace & Company
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 53/79
Copyright © 1999 by Harcourt Brace & Company
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 54/79
Copyright © 1999 by Harcourt Brace & Company
Why Beta Sheets?
for membrane proteins??• Genetic economy
• Alpha helix requires 21-25 residues per
transmembrane strand• Beta-strand requires only 9-11 residues
per transmembrane strand
•Thus, with beta strands , a given amountof genetic material can make a larger
number of trans-membrane segments
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 55/79
Copyright © 1999 by Harcourt Brace & Company
The Pore-Forming Toxins
• Lethal molecules produced by many
organisms
• They insert themselves into the host cellplasma membrane
• They kill by collapsing ion gradients,
facilitating entry by toxic agents, orintroducing a harmful catalytic activity
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 56/79
Copyright © 1999 by Harcourt Brace & Company
Colicins
• Produced by E. coli
• Inhibit growth of other bacteria (even
other strains of E. coli )• Single colicin molecule can kill a host!
• Three domains: translocation (T),
receptor-binding (R), and channel-forming (C)
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 57/79
Copyright © 1999 by Harcourt Brace & Company
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 58/79
Copyright © 1999 by Harcourt Brace & Company
Clues to Channel Formation
• C-domain: 10-helix bundle, with H8 and
H9 forming a hydrophobic hairpin
• Other helices amphipathic (Fig. 10.30)• H8 and H9 insert, with others splayed
on the membrane surface
• A transmembrane potential causes theamphipathic helices to insert!
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 59/79
Copyright © 1999 by Harcourt Brace & Company
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 60/79
Copyright © 1999 by Harcourt Brace & Company
Other Pore-Forming Toxins
• Delta endotoxin also possesses a helix-
bundle and may work the same way
• There are other mechanisms at work inother toxins
• Hemolysin from Staphylococcus aureus
forms a symmetrical pore• Aerolysin may form a heptameric pore -
with each monomer providing 3 beta
strands to a membrane-spanning barrel
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 61/79
Copyright © 1999 by Harcourt Brace & Company
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 62/79
Copyright © 1999 by Harcourt Brace & Company
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 63/79
Copyright © 1999 by Harcourt Brace & Company
Amphiphilic Helices
form Transmembrane Ion Channels • Many natural peptides form oligomeric
transmembrane channels
• The peptides form amphiphilic -helices• Aggregates of these helices form
channels that have a hydrophobic
surface and a polar center• Melittin (bee venom), magainins (frogs)
and cecropin (from cecropia moths) are
examples
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 64/79
Copyright © 1999 by Harcourt Brace & Company
Amphipathic Helices
• Melittin - bee venom toxin - 26 residues
• Cecropin A - cecropia moths - 37
residues• Magainin 2 amide - frogs - 23 residues
• See Figure 10.35 to appreciate helical
wheel presentation of the amphipathichelix
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 65/79
Copyright © 1999 by Harcourt Brace & Company
The Magainin Peptides
• Discovered by Michael Zasloff
• He noticed that incisions on Xenopus
laevis (African clawed frog) healedwithout infection, even in bacteria-filled
aquarium water
• He deduced that the frogs produced asubstance that protected them from
infection!
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 66/79
Copyright © 1999 by Harcourt Brace & Company
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 67/79
Copyright © 1999 by Harcourt Brace & Company
The Cecropins
• Produced by Hyalophora cecropia (the
cecropia moth - see Figure 10.36)
• Induced when the moth is challenged bybacterial infections
• These peptides are thought to form -
helical aggregates in membranes,creating an ion channel in the center of
the aggregate
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 68/79
Copyright © 1999 by Harcourt Brace & Company
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 69/79
Copyright © 1999 by Harcourt Brace & Company
Gap Junctions
Vital connections for animal cells
• Provide metabolic connections
• Provide a means of chemical transfer
• Provide a means of communication
• Permit large number of cells to act in
synchrony
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 70/79
Copyright © 1999 by Harcourt Brace & Company
Gap Junctions
• Hexameric arrays of a single 32 kD
protein
• Subunits are tilted with respect tocentral axis
• Pore in center can be opened or closed
by the tilting of the subunits, e.g. asresponse to stress
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 71/79
Copyright © 1999 by Harcourt Brace & Company
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 72/79
Copyright © 1999 by Harcourt Brace & Company
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 73/79
Copyright © 1999 by Harcourt Brace & Company
Ionophore AntibioticsMobile carrier or pore (channel)
• How to distinguish? Temperature!
• Pores will not be greatly affected by
temperature, so transport rates are
approximately constant over largetemperature ranges
• Carriers depend on the fluidity of the
membrane, so transport rates are highlysensitive to temperature, especially near the
phase transition of the membrane lipids
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 74/79
Copyright © 1999 by Harcourt Brace & Company
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 75/79
Copyright © 1999 by Harcourt Brace & Company
Valinomycin A classic mobile carrier
• A depsipeptide - a molecule with both
peptide and ester bonds
• Valinomycin is a dodecadepsipeptide
• The structure places several carbonyl
oxygens in the center of the ring structure
• Potassium and other ions coordinate the
oxygens• Valinomycin-potassium complex diffuses
freely and rapid across membranes
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 76/79
Copyright © 1999 by Harcourt Brace & Company
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 77/79
Biochemistry 2/e - Garrett & Grisham
8/11/2019 Biochem 10
http://slidepdf.com/reader/full/biochem-10 78/79
Copyright © 1999 by Harcourt Brace & Company
Gramicidin A classic channel ionophore
• Linear 15-residue peptide - alternating D & L
• Structure in organic solvents is double
helical• Structure in water is end-to-end helical
dimer
•
Unusual helix - 6.3 residues per turn with acentral hole - 0.4 nm or 4 A diameter
• Ions migrate through the central pore
Biochemistry 2/e - Garrett & Grisham
top related