The most common type of eye cancer in youngsters is called retinoblastoma. Four categories are used to categorise the disease. One classification is based on whether the condition affects one eye or both; these are referred to as unilateral and bilateral, respectively. Based on gene expression analysis, retinoblastomas can be classified into two types. Group 1 exhibits an invasive tumour pattern together with a variety of different types of retinal cells. Group 2 exhibits a distinct cone photoreceptor expression profile. RBBP9 is a protein that is involved in the human cancer process and is a binding partner of retinoblastoma susceptibility protein (Rb). LxCxE is the Rb binding motif found in the sequence of RBBP9. Yeast two-hybrid experiments revealed that RBBP9 interacts with Rb. RBBP9 is 21 kD in size, and its crystal structure has been investigated. There is evidence linking RBBP9 to pancreatic cancer. Pancreatic cancer cannot develop without the protein's serine hydrolase activity. Serine hydrolase activity works by phosphorylating Smad2/3 less, which in turn suppresses TGF-β antiproliferative signalling. Our goals in this study are to visualise the protein structure in PyMol, determine the nature of the protein (whether hydrophobic or hydrophilic), use the multiple alignment tool COBALT to check for protein conservation across other species, identify both chains (A & B) using PyMol, examine the interaction between 2QS9 and 7OEX (a protein that is very similar to 2QS9) in PyMol, perform multiple sequence alignment using clustal omega to determine the nature of the protein, and plot the Ramachandran plot to visualise energetically allowed region in BioPython and Saves server and molecular docking of 2QS9 and Topotecan using CB-DOCK2.
The most common type of eye cancer in youngsters is called retinoblastoma. Leukocoria, strabismus, buphthalmus, advanced intraocular tumour, extraocular tumour involving orbital tissue, and cellulitis are the main signs of the illness.Four categories are used to categorise the disease. One classification is based on whether the condition affects one eye or both; these are referred to as unilateral and bilateral, respectively. The other group, known as intraocular and extraocular, respectively, is dependent on whether the condition is present inside the eyeball or in structures outside the eyeball (1). Retinoblastoma affects 1 in 14,000–20,000 live births worldwide. Retinoblastoma occurs in 40% of bilateral cases and 60% of unilateral instances. The illustration of a healthy eye and an afflicted eye is shown below.The affected eye has cancerous cell starting from the retina. The genetic nature of the disorder can be germline or somatic. The causative gene of retinoblastoma is RB1 and most bilateral retinoblastomas are caused by germline pathogenic mutations in this gene. 10% to 15% of unilateral retinoblastomas result from germline pathogenic mutations whereas the remaining85-90% is caused by somatic changes (2).
As per gene expression profiling, there are two groups of retinoblastomas. Group 1 has a range of various retinal cell types and the tumor pattern in this one is invasive. Group 2 showed a unique expression profile of cone photoreceptor. Below are the examples of unilateral and bilateral retinoblastoma (3).
Unilateral retinoblastoma- One eye here has leukocoria which is the white pupillary reflex.
Bilateral Retinoblastoma- Both the eyes show leukocoria
One of the proteins which is a binding partner of retinoblastoma susceptibility protein (Rb) is RBBP9 and is important in the human cancer pathway. RBBP9 has LxCxE in its sequence which is the Rb binding motif. RBBP9 was shown to interact with Rb by yeast two-hybrid and co-immunoprecipitation experiments. Substitution of Glutamine for Leucine in this motif blocked the binding of Rb. The size of RBBP9 is 21 kD and the crystal structure has been studied. RBBP9 has been implicated in pancreatic cancer. The serine hydrolase activity of the protein is necessary for the development pancreatic carcinoma. The serine hydrolase activity functions by inhibiting TGF-β antiproliferative signaling through suppressing Smad2/3 phosphorylation (4).
Below given is the crystal structure of RBBP9:
Figure1:RBBP9 interaction with other Rb family protein: (Image taken from Sergey M. Vorobiev et al., 2012)
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