Yet more on reality's antidarwinian bias III

An "Exquisitely Designed" Enzyme that Maintains DNA Building Blocks
Evolution News & Views January 16, 2016 4:49 AM

It's molecular machine time, and today we'll be looking at a particularly amazing one. It's essential, it's "evolutionarily ancient," and it's unique. This machine, named ribonucleotide reductase, or RNR for short, is a beauty. News from MIT explains why your life depends on this machine:

Cell survival depends on having a plentiful and balanced pool of the four chemical building blocks that make up DNA -- the deoxyribonucleosides deoxyadenosine, deoxyguanosine, deoxycytidine, and thymidine, often abbreviated as A, G, C, and T. However, if too many of these components pile up, or if their usual ratio is disrupted, that can be deadly for the cell.

A new study from MIT chemists sheds light on a longstanding puzzle: how a single enzyme known as ribonucleotide reductase (RNR) generates all four of these building blocks and maintains the correct balance among them. [Emphasis added.]

The image shows the complex machine with active sites that precisely fit the four different building blocks. Its job is to take the ribonucleotides that make up RNA and turn them into the deoxyribonucleotides that make up DNA.

"There's no other enzyme that really can do that chemistry," she says. "It's the only one, and it's very different than most enzymes and has a lot of really unusual features."

In order for the machine's moving parts to work, one of several "effector molecules" has to fit into its special spot, like a key that opens a latch. This causes the enzyme to open up a "distant" active site and let the appropriate RNA building block in. Then, the enzyme latches it into place for its operation.

Depending on which of these effectors is bound to the distant regulatory site, the active site can accommodate one of the four ribounucleotide substrates. Effector binding promotes closing of part of the protein over the active site like a latch to lock in the substrate. If the wrong base is in the active site, the latch can't close and the substrate will diffuse out.

"It's exquisitely designed so that if you have the wrong substrate in there, you can't close up the active site," Drennan says. "It's a really elegant set of movements that allows for this kind of molecular screening process."

This four-in-one machine takes on four different shapes depending on whether the RNA nucleotide is A, G, C, or U. It sends out DNA's four, A, G, C, and T with the appropriate sugar deoxyribose instead of ribose (replacing an OH radical with a hydrogen atom, a "reduction" reaction). But that's not all this amazing machine does:

The effectors can also shut off production completely, by binding to a completely different site on the enzyme, if the pool of building blocks is getting too big.

RNR is a multi-tool if there ever was one. The effectors, the substrates and the active sites are all closely matched to the operation at hand, whether generating more DNA building blocks or regulating their supply in the cell. A paper from the Annual Review of Biochemistry (2007) puts it this way:

An intricate interplay between gene activation, enzyme inhibition, and protein degradation regulates, together with the allosteric effects, enzyme activity and provides the appropriate amount of deoxynucleotides for DNA replication and repair.

A lot of new building blocks are needed for repair and replication. You can see why this enzyme is essential for a cell when it divides or suffers stress.

The news item mentioned a latch, but another paper from 2015 in the Journal of Biological Chemistry speaks of a switch mechanism:

Ribonucleotide reductase (RNR) catalyzes the reduction of ribonucleotides to the corresponding deoxyribonucleotides, which are used as building blocks for DNA replication and repair. This process is tightly regulated via two allosteric sites, the specificity site (s-site) and the overall activity site (a-site). The a-site resides in an N-terminal ATP cone domain that binds dATP or ATP and functions as an on/off switch, whereas the composite s-site binds ATP, dATP, dTTP, or dGTP and determines which substrate to reduce.

It's like a surgical robot that has a clamp with an on-off switch. The switch (the effector) turns the machine on, opening up the distant active site and letting the appropriate substrate in. The enzyme then clamps down on the substrate and "reduces" it by replacing the oxygen radical with a hydrogen. When released, the DNA building block is ready for use, the effector switches the machine off, and the enzyme is ready for the next operation.

Somehow, when there are too many building blocks floating around in the cell, an effector binds to a different active site, disabling the machine. It's uncanny how each part seems to know what's needed and how to provide it. This involves feedback from the nucleus, where genes respond to the supply by either locking the RNR enzymes or making more of them.

Catherine Drennan on the MIT team calls this enzyme "evolutionarily ancient" and speculates about its origin.

Deoxyribonucleotides are generated from ribonucleotides, which are the building blocks for RNAs -- molecules that perform many important roles in gene expression. RNR, which catalyzes the conversion of ribonucleotides to deoxyribonucleotides, is an evolutionarily ancient enzyme that may have been responsible for the conversion of the earliest life forms, which were based on RNA, into DNA-based organisms, Drennan says.

She buys into the "RNA World" scenario for the origin of life, a view that is loaded with problems. RNR is an enzyme made of protein. Did a world of floating RNA fragments somehow build this complex, multi-part protein machine before DNA-based organisms existed? That makes no sense. A ribozyme with enough "code" for RNR would itself be impossibly complex to imagine forming by chance. It would have no way to translate that code into a polypeptide without a ribosome, also made of RNA and protein. Finally, even if by multiple miracles a primitive RNR appeared with its effectors and started cranking out product, the "RNA world" would have no idea what to do with a bunch of DNA building blocks floating around. Notably, Drennan's paper in eLife says nothing about any of this. Instead, it praises the "elegant set of protein rearrangements" performed by RNR.


RNR is one of a multitude of complex, highly-specific, multi-component machines with moving parts. Found in the simplest bacteria and archaea all the way up to human beings, it deserves better than to be treated like hopeful junk that arose by chance and found a job by accident. It deserves to be honored as an "exquisitely designed" molecular machine that performs an "intricate interplay" of functions vital to life, just like an intelligent designer would envision, plan, and create.

Patience's rights tossed under the bus in the lone star state?

The Arrogance of "Doctor Knows Best"
Wesley J. Smith January 15, 2016 2:19 PM

The Texas Advance Directive Act (TADA) allows a hospital bioethics committee and doctors to veto wanted life-sustaining treatment if they believe the suffering thereby caused is unwarranted -- with the cost of care always in the unspoken background. It is a form of ad hoc health care rationing -- death panels, if you will -- that place the moral values and opinions of strangers over those of the patient and family.

Futile care theory would even allow strangers to veto the contents of a patient's written and expressly stated advance directive.

Texas Right to Life (among others) has been an adamant opponent of the law, attempting to get it repealed. This effort has been impeded repeatedly by the Texas Catholic Conference (see my article here) perhaps because the state's Catholic hospital association likes the law. Texas Alliance for Life (TAL) often carries the Catholic Conference's water on this matter, in agreement on this issue, ironically, with the utilitarian bioethics movement.

Why? It's a bit of a puzzlement. I don't doubt, they think it is the right thing. But it should also be noted that hospitals benefit financially by refusing wanted but expensive treatment. Perhaps their social justice inclinations see limited resources as best spent on other patients.

In the wake of the Chris Dunn case, in which the patient -- conscience and aware -- clearly wanted life-sustaining treatment to continue, TAL defenders of futile care expose the "doctor knows best" arrogance of the futile care movement. From "Balancing the Rights of Patients and Doctors," in Public Discourse (my emphasis):

A person in possession of his mental faculties is not morally bound to choose treatments whose negative effects are disproportionate to any good that could come from them. By the law of transitivity, it would seem to follow that neither his doctor nor his surrogates are either. Some may say that patients are the only ones able to judge the proportionality of suffering due to life-sustaining treatments. In this case, those treatments decreased the ability of the patient to judge.

I have heard such excuses and rationalizations in futile care controversies again and again: The patient doesn't really know what is best; the family is acting on guilt; misplaced religious belief is forcing a wrong choice; they should leave such decisions to the "experts." Bah!

Besides, Catholic moral teaching -- at least, as I understand it -- allows the patient to decide when suffering being experienced supersedes the benefit being received. It does not give that decision to doctors or bioethicists. Thus, for example, St. John Paul II decided not to try to stay alive by any means necessary. He was not prevented from doing so by others as is done in futile care cases.

The article also exhibits some mendacity by omission when it discusses the refusal by other hospitals to take Dunn, while leaving out important facts:

It is telling that, even with the assistance of the hospital over several weeks to find another care provider, none would accept Chris's transfer, indicating that other doctors agreed with the attending physician's prognosis.

But patients caught up in futile care cases usually lose money for hospitals in our capitated funding system. Moreover, this whole Texas controversy began when Houston hospitals created a futile care policy and agreed to honor such determinations made by other institutions. Heads we win, tails you lose.

If continuing wanted treatment is the wrong thing to do, that should not be decided by a Star Chamber bioethics committee made up of colleagues who reflect corporate or institutional values, meeting in secret with no real transparency or accountability. Rather, if maintaining life when that is wanted is so egregious as to be inhumane, the controversy belongs in open court, with cross examination, an official record, and a right to appeal.


Bioethics committees have a very important role to play as mediating bodies in the event of treatment disputes. But they should never be empowered to become institutionally authorized, quasi-judicial death panels.

The Watchtower Society's commentary on Goodness.

GOODNESS:
The quality or state of being good; moral excellence; virtue. Goodness is solid through and through, with no badness or rottenness. It is a positive quality and expresses itself in the performance of good and beneficial acts toward others. The most common words for “good” in the Bible are the Hebrew tohv and the Greek a·ga·thosʹ; a·ga·thosʹ is usually used in a moral or religious sense.

Jehovah’s Goodness. Jehovah God is good in the absolute and consummate sense. The Scriptures say: “Good and upright is Jehovah” (Ps 25:8), and they exclaim: “O how great his goodness is!” (Zec 9:17) Jesus Christ, though he had this quality of moral excellence, would not accept “Good” as a title, saying to one who addressed him as “Good Teacher”: “Why do you call me good? Nobody is good, except one, God.” (Mr 10:17, 18) He thus recognized Jehovah as the ultimate standard of what is good.

When Moses asked to see His glory, Jehovah replied: “I myself shall cause all my goodness to pass before your face, and I will declare the name of Jehovah before you.” Jehovah screened Moses from looking upon his face, but as he passed by (evidently by means of his angelic representative [Ac 7:53]) he declared to Moses: “Jehovah, Jehovah, a God merciful and gracious, slow to anger and abundant in loving-kindness and truth, preserving loving-kindness for thousands, pardoning error and transgression and sin, but by no means will he give exemption from punishment.”—Ex 33:18, 19, 22; 34:6, 7.

Here goodness is seen to be a quality that involves mercy, loving-kindness, and truth but does not condone or cooperate in any way with badness. On this basis David could pray to Jehovah to forgive his sins ‘for the sake of Jehovah’s goodness.’ (Ps 25:7) Jehovah’s goodness, as well as his love, was involved in the giving of his Son as a sacrifice for sins. By this he provided a means for helping those who would want that which is truly good, and at the same time he condemned badness and laid the basis for fully satisfying justice and righteousness.—Ro 3:23-26.

A Fruit of the Spirit. Goodness is a fruit of God’s spirit and of the light from his Word of truth. (Ga 5:22; Eph 5:9) It is to be cultivated by the Christian. Obedience to Jehovah’s commands develops goodness; no man has goodness on his own merit. (Ro 7:18) The psalmist appeals to God as the Source of goodness: “Teach me goodness, sensibleness and knowledge themselves, for in your commandments I have exercised faith,” and, “You are good and are doing good. Teach me your regulations.”—Ps 119:66, 68.

Goodness Bestows Benefits. Goodness can also mean beneficence, the bestowing of beneficial things upon others. Jehovah desires to express goodness toward his people, as the apostle Paul prayed for the Christians in Thessalonica: “We always pray for you, that our God may count you worthy of his calling and perform completely all he pleases of goodness and the work of faith with power.” (2Th 1:11) Many are the examples of God’s abundant goodness to those who look to him. (1Ki 8:66; Ps 31:19; Isa 63:7; Jer 31:12, 14) Moreover, “Jehovah is good to all, and his mercies are over all his works.” (Ps 145:9) With a purpose he extends good to all, that his goodness may bring many to serve him and that they may thereby gain life. Likewise, any individual exercising goodness is a blessing to his associates.—Pr 11:10.

As servants of God and imitators of him, Christians are commanded to prove what is God’s good and perfect will for them (Ro 12:2); they are to cling to what is good (Ro 12:9), to do it (Ro 13:3), to work what is good (Ro 2:10), to follow after it (1Th 5:15), to be zealous for it (1Pe 3:13), to imitate what is good (3Jo 11), and to conquer evil with it (Ro 12:21). Their doing of good is to be especially extended to those related to them in the Christian faith; additionally, it is to be practiced toward all others.—Ga 6:10.


A Related Term. Similar to the Greek word for good (a·ga·thosʹ) is another word, ka·losʹ. The latter denotes that which is intrinsically good, beautiful, well adapted to its circumstances or ends (as fine ground, or soil; Mt 13:8, 23), and that which is of fine quality, including that which is ethically good, right, or honorable (as God’s name; Jas 2:7). It is closely related in meaning to good, but may be distinguished by being translated “fine,” “right,” “honest,” or “well.”—Mt 3:10; Jas 4:17; Heb 13:18; Ro 14:21.