[nasibeh]

Hi every body
My question is about Proteins/Aminoacids. I want to know why the isomers in proteins or aminoacids are exclusively "Isomer L"? In the other word, why there is no "Isomer D" in natural proteins/aminoacids?
Thanks alot

[Borek]

http://www.chemicalforums.com/index.php?topic=36284

[nasibeh]

Thanks for your attention. But I didn't got any of the answers you posted on my question. would you please introduce a refernce or website to me? maybe an article could help me in this regard. I am really confused .

[Borek]

Alphahydroxy's post summarizes the problem and gives interesting concepts to search for:

http://www.chemicalforums.com/index.php?topic=36284.msg138884#msg138884

even if only vaguely, it should give you a starting point.

Besides, one easy search with Google shows that statement

I want to know why the isomers in proteins or aminoacids are exclusively "Isomer L"?

is not 100% true.

http://www.google.com/search?q=d-amino+acids+in+living+organism

[renge ishyo]

The answer for why *most* amino acid isomers are "L" in proteins is easy enough, it is because amino acids/proteins are synthesized from DNA and natural DNA nuleotides are predominantly one isomer as well in natural DNA. Chiral molecules beget chiral molecules in chemical reactions, and so if the nucleotides of DNA are all of one type of isomer so will the amino acids and proteins directly synthesized from it be all of one type (see this source which describes this in a bit more detail with references: http://www.iscid.org/encyclopedia/Chirality). The "D" amino acids are relatively rare in nature, and I suspect these amino acids are post translationally modified by the bacteria that make use of them. The reason for believing this is that these particular amino acids are found in the cell walls of certain bacteria and perhaps a few species have found that enemy chemical compounds have a harder time destroying the bacteria if it has a modified cell wall with an "unfamiliar" amino acid.

The question of why the nucleotides of the DNA are mostly all of the same isomer is the real mystery, and it probably has to do with the coiled structure of the DNA itself. The DNA coils need to be heavily compressed to fit inside the tiny cell nucleus, and to do so requires that the helixes all "turn" in the same direction just like a slinky compresses easily because all its coils are lined up with one another; if you bent one of the coils out of shape even by a little bit it wouldn't compress properly. Likewise, if you had some coils turned in the other direction because its nucleotides were of the opposite chirality the helix wouldn't stack the same way and would bulge out at the side (see pictures of the artifically created A-DNA helix to see what I mean).  In fact, studies have produced artificial DNA from mixtures of nucleotides of varying chirality that support this notion, and you can see a picture of many of possible alternative DNA structures on the wiki and compare their attributes: http://en.wikipedia.org/wiki/Z-DNA

The predominant form of natural DNA is called B-DNA and forms a left handed helix. You might ask why not go with all Z-DNA to form a right handed helix? You might also ask why not go with a universe made predominately out of anti-protons and positrons as opposed to ours which favors protons and electrons predominantly? Who knows. That question is larger than Biology.

[Yggdrasil]

Life evolving from abiotic components is a relatively rare event.  Probably the first self-replicating chemical systems that arose just happened to utilize L-amino acids and D-sugars to produce their protein and nucleic acid components, and all of their descendants inherited the same basic replicative systems from these ancient ancestral forms of life.  This is basically an extreme example of technological lock in.  As an example, the "qwerty" keyboard is definitely not the most optimal configuration for a keyboard.  However, because it was the first widely adopted system, it has persisted for over a century because it is too hard to move away from it.

The answer for why *most* amino acid isomers are "L" in proteins is easy enough, it is because amino acids/proteins are synthesized from DNA and natural DNA nuleotides are predominantly one isomer as well in natural DNA. Chiral molecules beget chiral molecules in chemical reactions, and so if the nucleotides of DNA are all of one type of isomer so will the amino acids and proteins directly synthesized from it be all of one type (see this source which describes this in a bit more detail with references: http://www.iscid.org/encyclopedia/Chirality).

Although DNA codes for protein, the chirality of DNA is not what determines the stereochemistry of proteins.  What determines the stereochemistry of proteins are the molecules which assemble proteins: the tRNAs, the tRNA synthetases, and the ribosome.  Because these molecules directly select the amino acids that become incorporated into proteins, the structure of these protein, RNA, and ribonucleoprotein complexes are what determine the stereochemistry of proteins.

The question of why the nucleotides of the DNA are mostly all of the same isomer is the real mystery, and it probably has to do with the coiled structure of the DNA itself. The DNA coils need to be heavily compressed to fit inside the tiny cell nucleus, and to do so requires that the helixes all "turn" in the same direction just like a slinky compresses easily because all its coils are lined up with one another; if you bent one of the coils out of shape even by a little bit it wouldn't compress properly. Likewise, if you had some coils turned in the other direction because its nucleotides were of the opposite chirality the helix wouldn't stack the same way and would bulge out at the side (see pictures of the artifically created A-DNA helix to see what I mean).  In fact, studies have produced artificial DNA from mixtures of nucleotides of varying chirality that support this notion, and you can see a picture of many of possible alternative DNA structures on the wiki and compare their attributes: http://en.wikipedia.org/wiki/Z-DNA

The predominant form of natural DNA is called B-DNA and forms a left handed helix. You might ask why not go with all Z-DNA to form a right handed helix? You might also ask why not go with a universe made predominately out of anti-protons and positrons as opposed to ours which favors protons and electrons predominantly? Who knows. That question is larger than Biology.

DNA molecules composed of solely L-sugars (as compared to D-sugars) still forms well structured helices.  Chemists have actually been able to artificially synthesize such DNA molecules and characterize their properties (1).  Their results show that such "mirror-image" DNA retains the same conformation, structure, and properties except for the fact that it is a literal mirror image of the normal DNA helix.  So, this explains why DNA consists of nucleotides of the same chirality (either all D- or all L-enantiomers).  The fact that D-DNA arose instead of L-DNA is likely just by chance since it seems like either could function equally well.

Also A-DNA is not artificial and it can be packed efficiently into small spaces.  For example, Bacillus subtitlis and other spore-forming bacterial package their DNA as A-DNA when they form spores (2).

¹Urata H et al. J. Am. Chem. Soc. 1991, 113:8174–8175, doi:10.1021/ja00021a057
²Setlow P. J Bacteriol. 1992, 174: 2737–2741, PMCID: PMC205922

[renge ishyo]

The question of whether the chirality was created first by either the RNA or DNA is rather like a "chicken or the egg" question. We can argue that DNA ultimately is responsible for the chirality since DNA originally creates the RNAs that interact with the amino acids and the ribosomes to make the proteins. However, when DNA is replicated it is carried out by proteins which were in turn synthesized originally by the RNA which suggest that maybe RNA and proteins came before DNA. Either way the chirality of the nucleotides is passed on the chirality of the amino acids which in turn pass on the chirality to the proteins. That much at least I can see as being reasonable (but of course there are still hardcore protein lovers who will say it was proteins that came first and who will disagree with me! Although the evidence indicates that this is far less likely than having DNA or RNA as the original molecule).

I don't know why B-DNA is favored over Z-DNA (Z-DNA is the helix you describe where the chirality on the nucleic acids is exactly opposite so that the only observable difference is that the helix turns in the opposite direction to our own). In terms of their packing properties these two should be equally acceptable and it is strange then that only the B-form predominates. The A DNA, like the "D" amino acids in certain bacteria, are so far only revealed to be present in certain bacteria and may be seen as bacterial specializations or lost remnants of the evolutionary choice that eventually weeded things down to B-DNA depending on who you talk to. There are always exceptions to the rule 

This is why I bring up the whole proton/electron universe vs. the anti-proton/positron universe. Our universe could conceivably exist either way, just in the anti-proton/positron universe the signs on the electric charges would all be switched. So why do we have a proton/electron/B-DNA universe rather than an anti-proton/positron/Z-DNA universe that is identical in almost all respects, but "rotates" in the opposite direction? This question seems to be at the core of the mystery.

[Yggdrasil]

The question of whether the chirality was created first by either the RNA or DNA is rather like a "chicken or the egg" question. We can argue that DNA ultimately is responsible for the chirality since DNA originally creates the RNAs that interact with the amino acids and the ribosomes to make the proteins. However, when DNA is replicated it is carried out by proteins which were in turn synthesized originally by the RNA which suggest that maybe RNA and proteins came before DNA. Either way the chirality of the nucleotides is passed on the chirality of the amino acids which in turn pass on the chirality to the proteins. That much at least I can see as being reasonable (but of course there are still hardcore protein lovers who will say it was proteins that came first and who will disagree with me! Although the evidence indicates that this is far less likely than having DNA or RNA as the original molecule).

Good point.

I don't know why B-DNA is favored over Z-DNA (Z-DNA is the helix you describe where the chirality on the nucleic acids is exactly opposite so that the only observable difference is that the helix turns in the opposite direction to our own).

This is not a correct description of Z-DNA.  Z-DNA is not a general term for DNA that forms a left handed helix.  The DNA molecules in Z-DNA have the same chirality as the DNA molecules in B-DNA  (i.e. it is composed of nucleotides with D-sugars).  Furthermore, Z-DNA does not simply turn in the opposite direction as B-DNA; there are huge structural differences between the two.  For example, whereas the structure of B-DNA repeats every base pair, Z-DNA's is composed of 2bp repeats.  There are 12 bp per turn in Z-DNA compared to 10.5 bp in B-DNA and Z-DNA is longer and slightly less wide.  Probably the biggest difference can be seen in the conformation of the nucleotide.  In B-DNA, all of the bases have their Watson-Crick faces pointing away from the sugar ring (in the anti-configuration).  However, in Z-DNA many of the bases will be in the syn conformation, with the glycosidic bond rotated 180^o, turning the Watson-Crick face of the base toward the sugar ring.  There are many other difference between B-DNA and Z-DNA than just simply the directions in which the helices turn.  If you made a mirror image of B-DNA, it would not be Z-DNA.

Why is Z-DNA uncommon?  Double stranded DNA of almost any sequence will spontaneously form a B-form helix in water.  However, only double stranded DNA with specific GC-rich sequences can form a Z-form helix, and some form it only transiently.  So, the prevalence of B-DNA is explained by simple thermodynamics.  For most double stranded DNA sequences, a B-form helix is the lowest energy structure.  There is nothing intrinsically special about the B-form helix, because double stranded RNA forms an A-form helix and RNA/DNA hybrids form a different type of helix.  These structures are merely governed by the energetics of the bond angles, bond lengths, etc. involved in each structure.

[renge ishyo]

Yep, that's right Z-DNA is made out of the same chirality of nucleotides as B-DNA, so it was not the helix I meant to speak about. In fact, this means I do not know the name of the helix which is formed where all the chirality is swapped for each nucleotide.

[BetaAmyloid]

Well, I am not specified in this area, but I can tell you that everything has a specific shape, respectively. So, knowing that, if a protein was not in the "Isomer L" position, and was changed to an "Isomer D" position, then it would now longer be a protein, but another molecule. I was discussing this with a teacher, but it seems that even if you switch the position of an isomer, although it has the same "shape" as the original isomer, it becomes and acts in a totally different way.

Hope this helps,
The Cancer Curer

[JGK]

Well, I am not specified in this area, but I can tell you that everything has a specific shape, respectively. So, knowing that, if a protein was not in the "Isomer L" position, and was changed to an "Isomer D" position, then it would now longer be a protein, but another molecule. I was discussing this with a teacher, but it seems that even if you switch the position of an isomer, although it has the same "shape" as the original isomer, it becomes and acts in a totally different way.

I'm afraid you are incorrect in this statement. The individual amiono acids exhibit d/l isomerism, not the protein molecule and if the protein molecule was made up of d or l isomers it would still be a protein as the chemical composition would be identical.

d/l isomersim affects spacial structure and activity only, not chemical structure/composition.