Biomedical Engineering Reference
In-Depth Information
(a)
(b)
Figure 3.1
(See companion CD for color igure.)
.Biological.molecular.machines..(a).The.F
1
.domain.of.the.F
o
−F
1
.ATP.syn-
thase..Rotation.of.the.central.stalk.(green).in.120°.steps.causes.conformational.changes.in.the.β.domains.(red),.
which. cycle. among. three. states. with. distinct. afinities. for. ATP. and. ADP.. (Produced. from. PDB. 1E79.). (b). The.
ribosome.is.a.factory.that.reads.information.from.mRNA.and.catalyzes.the.synthesis.of.polypeptide.chains..It.
is.composed.of.a.large.(blue).and.a.small.(green).subunit.that.clamp.together.around.an.mRNA.molecule.(not.
shown)..More.than.half.of.the.ribosome,.including.the.catalytic.site,.consists.of.RNA.(orange)..(Produced.from.
PDBs.2WDK.and.2WDL.)
sequences.. Amino. acid. building. blocks. are. added. one-by-one. to. the. end. of. a. growing.
polypeptide. chain.. Thanks. to. the. ribosome,. heritable. genetic. information. is. able. to.
direct. the. creation. of. information-rich. polymers. that. fold. speciically. and. perform.
precise.functions..Bulk.synthetic.chemical.peptide.synthesis.methods.fall.far.short.of.the.
eficiency.and.speciicity.(about.1.error.per.10,000.amino.acids.[Ellis.and.Gallant.1982]).of.
the.ribosome..The.1974.Nobel.Prize.in.Medicine.and.the.2009.Nobel.Prize.in.Chemistry.
were.both.awarded.for.studies.of.the.ribosome.
Often,.the.activity.or.substrate.preference.of.a.natural.enzyme.can.be.modiied.drastically.
by.mutating.even.a.single.active.site.amino.acid.by.chemical.intuition.(reviewed.by.Toscano.
et. al.. [2007]).. While. enzymes. with. remarkably. different. properties. can. be. generated. by.
this.type.of.rational.active.site.redesign,.the.creation.of.artiicial.enzymes.to.perform.any.
desired.reaction.under.any.process.conditions.will.require.more.general.approaches.
3.2 Directed Evolution
In.the.absence.of.a.method.to.create.designer.enzymes.from.scratch,.nature.has.been.our.
only.source.of.catalytic.nanomachines..For.centuries,.domestication.of.biological.organisms.
and.their.enzymes.have.provided.humanity.with.a.way.to.produce.valuable.products.like.
beer.and.cheese..However,.natural.enzymes.have.evolved.to.meet.the.speciic.requirements.
of.their.host.cells,.and.the.demands.of.human.industrial.or.health.applications.are.often.
quite. different. than. those. of. any. natural. environment.. To. modify. natural. enzymes. to.
