Efficiency of enzymes

How long will a reaction take to complete without enzymes?
Well, some reactions will only complete in about 2.3 billion years without them...
Without Enzyme, Biological Reaction Essential To Life Takes 2.3 Billion Years

But enzymes don't just pop into existence, not even under the BEST pre-biotic synthesis scenarios. Enzymes are produced and folded into the correct conformation by.... other enzymes... controlled by.... biomolecular machines and a genetic code..

More about the efficiency of enzymes:
Biochemistry: Enzymes under the nanoscope

Quote:

Small-scale interactions of substrates with an enzyme's active site — over distances smaller than the length of a chemical bond — can make big differences to the enzyme's catalytic efficiency. When Richard Feynman died in 1988, he left behind the following words on his blackboard: "What I cannot create, I do not understand." His message certainly resonates with protein engineers.

Enzymes are guided into their correct 3D configuration by other enzyme complexes known as chaperones (part of the heat-shock protein family). What happens if the configurations are not right? Scientists determined that some enzymes, as in the case of ketosteroid isomerase, are so precisely folded for their particular ligand/substrate that if it the 3d conformation was off by even 10 picometers (10^12 meters) it would lose its efficiency. Firstly, the conformation has to be just right to tightly bind the ligand into the pocket of the protein, then another mechanism (built in property of the enzyme) is responsible the transfer of electrons in order to catalyze and complete the enzymatic reaction. Our current best efforts at designing artificial enzymes are (from the article) “still tens of billions of times smaller than those of many enzymes.”

The ribosome is a super complex of enzymes, a molecular machine responsible for the building of polypeptide chains which in turn are folded into active proteins by chaperone complexes.
Problems do occur, but checks and balances are present. For example:
Side-chain recognition and gating in the ribosome exit tunnel
At the exit tunnel of the ribosome, it is hypothesized that there are gate and latch mechanisms with active valves controlling the exit of polypeptides. The researchers conclude that these mechanisms play a role in the regulation of "nascent chain exit and ion flux". Sort-off like a final checkpoint.



As already seen, without enzymes, reactions that are crucial to life might take billions of years to complete. Small changes (10 picometers) in the 3D structure of an enzyme can also negatively affect the function of an enzyme.
So how are enzymes folded into their active conformation?

Chaperonins: Two-stroke, two-speed, protein machines

Article:
Setting the chaperonin timer: A two-stroke, two-speed, protein machine
From the article:

Quote:

Protein machines and their man-made, macroscopic counterparts share several common attributes, e.g., concerted, coordinated movements, cyclical operation, and energy transduction. These machines are seldom reversible because each cycle generally involves at least one irreversible step, e.g., the consumption of fuel. Often these machines operate at variable speed, a plethora of timing devices adjusting the cycle speed in response to demand. An exemplary bipartite protein machine is the chaperonin system, typified by GroEL and GroES from Escherichia coli. GroEL is composed of 2 heptameric rings, stacked back to back, which, in the presence of GroES, operate out of phase with one another in the manner of a 2-stroke, reciprocating motor (1, 2). Driven by the hydrolysis of ATP, the chaperonin proteins function as a biological simulated annealing machine (3, 4), optimizing the folding of their substrate proteins (SPs) whose passage to biologically functional conformations is thus assured.

Quote:

The picture of the chaperonins that emerges from our work is that of a machine equipped with a timer, the trans ring, poised to respond to the appearance of SP [substrate protein inside the cavity] but otherwise idling in a quiescent state. We note that Nature’s design of this 2-speed protein machine minimizes the hydrolysis of ATP in the absence of SP. However, it maximizes the number of turnovers and minimizes the residence time available to the encapsulated SP to reach the native state, design principles well suited to the operation of an iterative annealing device.

Partial part and dynamics of the system.
Nice video of how it operates

Machines folding machines into place. Beautiful...