All-D World

From: Jacob Keller
Date: 15 February 2012 18:28


So who out there wants to start an all-D microbial culture by total
synthesis, a la the bacterium with the synthetic genome a while back?
Could it work, I wonder? I guess that would be a certain benchmark for
Man's conquest of nature.

JPK

ps maybe if there is a broadly-acting amino-acid isomerase or set of
isomerases of appropriate properties, this could be helpful for
getting the culture started--or even for preying on the L world?



On Wed, Feb 15, 2012 at 12:17 PM, David Schuller wrote:
> On 02/15/12 12:41, Jacob Keller wrote:
>
> Are there any all-D proteins out there, of known structure or
> otherwise? If so, do enantiomer-specific catalyses become inverted?
>
> JPK
>
> What do you mean by "Out There"? If you mean in the PDB, then yes.  As of
> two weeks ago, there are ~ 14 racemic structures deposited; most in space
> group P -1, with one outlier in space group I -4  C 2. This includes RNA,
> DNA, and PNA, but 6 entries are actually protein. The longest is over 80
> residues.
>
> Theoretically, enantiomer-specific catalysis ought to be inverted, but most
> of the structures solved are not enzymes. kaliotoxin, plectasin, antifreeze
> protein, monellin, villin, and a designed peptide.
>
> On the other hand, if by "out there" you meant in nature outside of
> biochemistry and organic chemistry labs; then no, I am not aware of any
> all-D proteins. There are a few protein/peptides which include a small
> number of D-residues, which is marked up to nonribosomal synthesis.
>
> The first paper I managed to Google:
> http://jb.asm.org/content/185/24/7036.full
> Learning from Nature's Drug Factories: Nonribosomal Synthesis of Macrocyclic
> Peptides
> doi: 10.1128/JB.185.24.7036-7043.2003 J. Bacteriol. December 2003 vol. 185
> no. 24 7036-7043
>
> If racemic crystallization isn't exciting enough for you, look into
> quasi-racemic crystallization.
>
>
> On Wed, Feb 15, 2012 at 8:05 AM, David Schuller wrote:
>
> Wukovitz & Yeates (1995) Nature Struc. Biol. 2(12): 1062-1067
> predicts that the most probable space group for macromolecular
> crystallization is P -1 (P 1-bar). All you have to do to try it out is
> synthesize the all-D enantiomer of your protein and get it to fold properly.
>
>
> On 02/14/12 18:36, Prem Kaushal wrote:
>
>
> Hi
>
> We have a protein that crystallized in P21212 space group. We are looking
> for some different crystal forms. We tried few things did not work. Now we
> are thinking to mutate surface residues. Anybody aware of any software which
> can predict the mutations that might help in crystallizing protein in
> different space group, please inform me.
>
> Thanks in advance
>
> Prem
>
>
> --
> =======================================================================
> All Things Serve the Beam
> =======================================================================
>                                David J. Schuller


--
**************************

----------
From: Ho,Shing

The structure of an all D-amino acid version of the HIV-1 protease was
solved in 1992 (see Milton, Milton, and Kent, 1992, Science,
256:1445-1448). The D-enzyme was seen to have a structure that is the
mirror image of the L-enzyme, and showed specificity for the enantiomeric
form of the chiral substrate.

________________________________________

P. Shing Ho, PhD
Professor & Chair

----------
From: William G. Scott


Hi Jacob:

After giving this a great deal of reflection …..
I realized that you would face the same paradox that
God had to resolve six thousand years ago at the Dawn of
Creation, i.e., He needed D-deoxyribose DNA to code for L-amino acid
proteins, and vice versa.  Likewise, you would probably be faced
with a situation where you need L-deoxyribose DNA to code for D-amino
acid proteins, so once again, you need a ribozyme self-replicase to
escape the Irreducible Complexity(™).  (The Central Dogma at least is achiral.)

At least it can be done six thousand years, which isn't unreasonable for
a Ph.D. thesis project (especially when combined with an M.D.), and you,
unlike Him, have access to a Sigma catalogue.

All the best,

Bill


----------
From: Katherine Sippel


Well if you think about it technically God produced plants within three days which if far too little work for a thesis. Maybe it could count as preliminary results for one aim of a thesis proposal so it might be enough to get PhD candidacy depending on how demanding your committee is. You could always propose the remaining 5999 years and 362 days to do a massive data mining initiative.

Thanks for the laugh. I needed it.

Katherine

----------
From: Jacob Keller


G-d is right-handed, so to speak:

Ex 15:6 "Thy right hand, O LORD, is become glorious in power: thy
right hand, O LORD, hath dashed in pieces the enemy."

Since we are made in His image, and our (chiral) molecules are the
cause of making most of us right-handed, which enantiomer to use was
not a real choice but rather flowed logically from His (right-handed)
Essence. Our chirality is dictated by His, whatever that means!

JPK

----------
From: Eric Bennett

Jacob,

I wish it were that cheery.  Do not forget the darker side of history.

The prefix "L-" stands for levorotary.  The "levo" comes from the Latin wording for "left side".  Left handedness is also known as sinistrality, from the Latin "sinistra" which also meant the left side, but over time took on the connotations that we currently associate with the word "sinister".  The latter word, of course, is generally associated with dark and evil.  It is therefore erroneous to attribute the L amino acid to the Almighty.  The L amino acid is in fact a diabolical corruption of cellular processes that begin with the D-nucleotide ("D-" meaning rotating to the right, but derived from dexter, meaning dextrous and skillful).  The instrument which causes this perversion of God's perfect righteousness into a sign of evil deserves our strongest moral condemnation... I am referring, of course, to that devilish piece of cellular machinery known as the ribosome.

The discovery of the ribosome was a significant blow to the success of what Charles Baudelaire famously called the devil's greatest trick.  For years now, his acolytes have attempted to hide the truth about the ribosome by referring to its work with the neutral, innocent-sounding phrase "translation".  Don't be fooled, but instead pray for the development of the next generation of ribosome inhibitors, or at least dissolve the current generation in holy water before ingesting.

-Eric

----------
From: Frank von Delft 

I believe Eric is paraphrasing Genesis 3.  It's all the serpent's fault.

http://www.ic.unicamp.br/~stolfi/PUB/misc-misc/GenesysParody.html <http://www.ic.unicamp.br/%7Estolfi/PUB/misc-misc/GenesysParody.html>

Wukovitz&  Yeates (1995) Nature Struc. Biol. 2(12): 1062-1067