Interpretation:
Using the active model for Niemann-Pick C1, the structure of the sterol-binding pocket, and the interaction involved in cholesterol binding should be described.
Concept Introduction:
Niemann-Pick C1 protein (NPC1) is a endosomal membrane protein required for transport of LDL derived cholesterol into cells. NPC1 consists with a sterol sensing domain (SSD) which is similar to SSDs in protein responsible for cholesterol biosynthesis, uptake and signaling. NPC1’s SSD forms a cavity that is accessible from both luminal bilayer leaflet and the endosomal lumen. According to the computational modeling, it is suggested that this cavity is large enough to be occupied by one cholesterol molecule.
Cholesterol is transported as cholesterol esters which are packed in lipoproteins such as low density lipoproteins (LDL). LDL is transported to endosomes and lysosomes and they are subjected to lipolysis by lipase. Then released cholesterol is bound one molecule at a time to soluble intraliposomal protein, Niemann-Pick C2 (NPC2). NCP2 bound cholesterol is then transferred to another pocket in N-terminal domain of NPC1. Here the cholesterol is bound in opposite orientation. N terminal domain of NPC1 is connected via a proline rich region to transmembrane segment 1 (TM1).
Want to see the full answer?
Check out a sample textbook solution
Chapter 24 Solutions
Biochemistry
- This question should be answered with two or three sentences using relevant biochemical vocabulary.arrow_forwardGout is a medical condition usually caused by a deficiency of the salvage enzyme hypoxanthine-guanine phosphoribosyltransferase. Uric acid accumulates in the joints and causes pain, inflammation, and in advanced disease gouty tophi. Allopurinol, an inhibitor of the enzyme xanthine oxidase, is used to treat chronic gout. Explain briefly the biochemical basis for this treatment.arrow_forwardPlease answer asap and in short First question onlyarrow_forward
- Briefly explain why allosteric inhibition is an example of negative heterotropic cooperativity and allosteric activation an example of positive heterotropic cooperativity?arrow_forwardOn Dimyristoyl phosphatidylserine, Palmytoyl-Oleoyl Phosphatidylcholine and Sphingomyelin, What is the capacity of each of these to form hydrogen bonds with its neighboursarrow_forwardusing specific examples explain the biochemical significance of saturated and unsaturated fatty acids.arrow_forward
- MATHEMATICAL The hydrolysis of a phenylalanine-containing peptide is catalyzed by -chymotrypsin with the following results. Calculate KM and Vmax for the reaction. PeptideConcentration(M)Velocity(Mmin1)2.51045.010410.010415.01042.21065.81065.91067.1106arrow_forwardREFLECT AND APPLY An inhibitor that specifically labels chymotrypsin at histidine 57 is N-tosylamido-L-phenylethyl chloromethyl ketone. How would you modify the structure of this inhibitor to label the active site of trypsin?arrow_forwardUsing the ActiveModel for aldose reductase, describe the structure of the TIM barrel motif and the structure and location of the active site.arrow_forward
- MATHEMATICAL Determine the values of KM and Vmax for the decarboxylation of a -keto acid given the following data. substrateconcentration(molL1)Velocity(mMmin1)2.5001.0000.7140.5260.2500.5880.5000.4170.3700.256arrow_forwardCrystal structures exist for three neurokinin-1 (NK1) ligand complexes with the following pdb codes (6hll, 6hlo, 6hlp) For each of the three crystal structures identify four amino acids in the NK1 binding site that contact the ligand indicating both the residue type in three letter code and the residue number. One of the chose amino acids should form a hydrogen binding interaction to the ligand, state which functional group the amino acid utilises in each casearrow_forwardCalculate the actual, physiological AG for the reaction Phosphocreatine + ADP = creatine + ATP at 37 °C, as it occurs in the cytosol of neurons, where [phosphocreatine] = 4.7 mM, [creatine] = 1.0 mM, [ADP] = 0.73 mM, and [ATP] = 2.6 mM. Standard Free Energies of Hydrolysis of Some Phosphorylated Compounds Phosphorylated compound AGʻ° (kJ/mol) phosphoenolpyruvate -61.9 phosphocreatine -43.0 ADP (→ AMP + P;) -32.8 ATP (→ ADP + P;) -30.5arrow_forward
BiochemistryBiochemistryISBN:9781305577206Author:Reginald H. Garrett, Charles M. GrishamPublisher:Cengage Learning
BiochemistryBiochemistryISBN:9781305961135Author:Mary K. Campbell, Shawn O. Farrell, Owen M. McDougalPublisher:Cengage Learning