User:Girlwholovesscience/Hemoglobin

I decided to look more into the globin family and am adding to the page about cytoglobins. You can see what is already there: Cytoglobin

But the things I am adding I will put on this sandbox  :)

Because it was originally discovered in the hepatic stellate cells during fibrosis, cytoglobin was originally called "stellate cell activated protein" or STAP.. Cytoglobin is actually found in nearly every tissue of the body. Its expression is unregulated during hypoxia, and transcription is driven by HIF-1. This contributes to our understanding of why it is involved in regulating oxidative stress. [https://pmc.ncbi.nlm.nih.gov/articles/PMC8799389/#F0005] It was noticed specifically during liver fibrosis.

[https://pmc.ncbi.nlm.nih.gov/articles/PMC8799389/#F0005]

[https://www.sciencedirect.com/science/article/pii/S0162013404003514?via%3Dihub]

Structure:

·      Has 30-40% sequence homology with myoglobin

·      It is a hexacoordinate heme protein.

·      Hexacoordinate means it coordinates with the distal histidine(E7) as well, until the ligand binds, then the distal histidine is pushed off. The E7His is considered an "endogenous ligand." The binding kinetics are relatively slow because of the need to displace the distal E7 histidine before the gas ligand (NO or O₂ can bind). [https://www.sciencedirect.com/science/article/pii/S0162013404003514?via%3Dihub]

Diagram of how the heme group in cytoglobin interacts with the surrounding amino acids of the globin protein. Normally, the iron is coordinated with histidine residues on both sides. The HisE7 must be dissociated in order for oxygen to bind.

·      Has extensions of 20 amino acids at both the n and c terminus [https://www.sciencedirect.com/science/article/pii/S0162013404003514?via%3Dihub]

·      Its o2 affinity is redox dependent (science direct)

·      Its binding affinity, which is between .5 and 3 Torr is less than that of hemoglobin and myoglobin

Possible functions: although the functions of cytoglobin are still being explored by scientists, possible functions include

·      Facilitate oxygen distribution and transportation among tissues that don’t express myoglobin.

·      Supply enzymes with oxygen that need them for reactions, such as collagen production, supplying oxygen to the collagen prolyl-hydroxylases.

·      Binds to NO and forms nitrate (dioxygenation) - it does this faster than hemoglobin.

but it can also go the opposite way and help form NO, which is important for regulating many physiological functions especially in the vascular system.

·      Could play a role in oxygen storage during hypoxia from ischemia.

·      Scavenges reactive nitrogen species

[https://pmc.ncbi.nlm.nih.gov/articles/PMC8799389/#F0005}

possible image: show the reaction of how it has to become uncoordinated with the distal His in order to coordinate with oxygen. I could also show how the Cys38-Cys83 disulfide bond affects cytoglobins affinity to oxygen.

Structure

Cytoglobin has 30-40% sequence homology with myoglobin, and has a similar oxygen binding affinity. One of the major differences is the presence of a 20 amino acids extension at both the n and c terminus.

Cytoglobin is a hexacoordinate heme protein. The heme iron in coordinated with histidine residues on both sides, HisF8 and HisE7. The HisE7 is considered to be an "endogenous ligand." In order for oxygen or another gaseous ligand to bind, the HisE7 must dissociate from the iron, making the binding kinetics relatively slow.

In an oxidizing environment, a disulfide bond between Cys38 and Cys83 of the protein forms and causes a conformational change to move HisE7 out of the way, allowing oxygen to bind. Thus, oxygen binding is dependent on the redox state of the tissue.