Structural analysis on the abnormal elongated hemoglobin "hemoglobin Geneva".Wiwanitkit V. (2005) Nanomedicine 1: 216-8.Abstract: Hemoglobin variants in which a frameshift results in chain elongation are not common. Hemoglobin Geneva (Hb Geneva) is an unstable hemologin with abnormal elongation. This hemoglobinopathy is known for its high instability. Concerning the pathogenesis of Hb Geneva, the data indicate a change in codon 114 from CTG (Leu) to -GG that results in a frame shift and the presumed synthesis of an abnormal beta-chain that is 156 residues long with a completely different C-terminal amino acid sequence. This abnormality causes a frame shift, which results in elongation of the beta-chain amino acids. A bioinformatic analysis was performed to study the secondary and tertiary structures of those abnormal amino acid sequences. A computer-based study for protein structure modeling was performed. According to this study, the secondary structure analysis of the Hb Geneva showed many defects in helix and strand of the Hb Geneva compared with normal beta-globin chains. On the basis of this information, the main alteration in the Hb Geneva might be due to these aberrations. With regard to the tertiary structure, the deterioration of folds, accompanied by the aberration in secondary structure of globin in Hb Geneva can be identified.CHEM-342 Introduction to BiochemistryFinal Examination - Individual (Part I)Friday, 25 May 20073:30 – 6:30 PM H. B. White - InstructorYour Name____________________________The tendency in course examinations is to pose thequestion, "How much do you remember of what hasbeen covered?" rather than, "What can you do withwhat you have learned?" Richard Felder 1995Average = 52.4, Range = 19 - 81 out of 75 (incl. bonus points), N=43Important - Please read this before you turn the page.$ This examination will assess your learning, problem-solving skills, and ability tocommunicate clearly. It is intended to be challenging even to the best students in theclass. Writing reflects how you think. Among the “right answers” I will read, somewill be better than others because they show greater depth of understanding, avoidextraneous or inaccurate information, provide a more logical structure, use appropriateexamples, and choose words with precision. Better quality answers will receivehigher marks. Therefore organize your thoughts before you write or draw. Strive towrite not that you may be understood, but rather that you cannot possibly bemisunderstood. Stream of consciousness answers are rarely well organized or clearlypresented.$ This examination emphasizes work done in this course since Spring Break; however,knowledge is not so conveniently compartmentalized. Therefore, you should feel freeto use any relevant example from your experience, if it is appropriate.$ There are 8 pages to this part of the examination (counting this cover page and theinformation sheet at the back). Please write your name on each page. Feel free to usethe backs of pages, if you need more space.$ Part I (75 points) This individual part of the examination, includes 7 problems andshort essay questions. Also, you can obtain up to 10 additional points from two bonusquestions.Part II (25 points) The group part of the examination will require you to deal with newinformation collaboratively.$ If you complete Part I early, you may leave the room for a break and return 208 GoreHall at or before 5:15 PM when the group part of the exam begins.$ You may refer to your notes, course reader, handouts, or graded homeworkassignments. $ Attempt to draw a picture or diagram as part of your answer to every question.$ Graded examinations may be picked up Wednesday morning, 30 May.$ Have a productive and safe Summer.CHEM-342 Introduction to Biochemistry Your Name ____________________________________Final Examination Individual Part, 25 May 2007 Page 31. (25 Points Total) Analysis of Hemoglobin VariantsRoutine electrophoretic surveys of human blood samples have revealed hundreds of varianthemoglobins. Most are rare and differ from normal hemoglobin by a single amino acidreplacement. Some like HbS produce severe clinical problems; others produce no ill effects.This question deals with two different hemoglobin variants that affect the -chain.Hemoglobin-G Coushatta was reported in two groups of Native Americans and is harmless.Hemoglobin Southampton was discovered in England and causes severe hemolytic anemia.Each variant has been purified and its sequence determined. The 146 amino acid sequencefor the normal human hemoglobin -chain is given below for reference in the questions thatfollow. 1 10 20 30 NH3-Val-His-Leu-Thr-Pro-Glu-Glu-Lys-Ser-Ala-Val-Thr-Ala-Leu-Trp-Gly-Lys-Val-Asn-Val-Asp-Glu-Val-Gly-Gly-Glu-Ala-Leu-Gly-Arg-40 50 60Leu-Leu-Val-Val-Tyr-Pro-Trp-Thr-Gln-Arg-Phe-Phe-Glu-Ser-Phe-Gly-Asp-Leu-Ser-Thr-Pro-Asp-Ala-Val-Met-Gly-Asn-Pro-Lys-Val-70 80 90 Lys-Ala-His-Gly-Lys-Lys-Val-Leu-Gly-Ala-Phe-Ser-Asp-Gly-Leu-Ala-His-Leu-Asp-Asn-Leu-Lys-Gly-Thr-Phe-Ala-Thr-Leu-Ser-Glu- 100 110 120Leu-His-Cys-Asn-Lys-Leu-His-Val-Asp-Pro-Glu-Asn-Phe-Arg-Leu-Leu-Gly-Asn-Val-Leu-Val-Cys-Val-Leu-Ala-His-His-Phe-Gly-Lys- 130 140 146 Glu-Phe-Thr-Pro-Pro-Val-Gln-Ala-Ala-Tyr-Gln-Lys-Val-Val-Ala-Gly-Val-Ala-Asn-Ala-Leu-Ala-His-Lys-Tyr-His-COOHemoglobin was aminoethylated in a reaction that modifies cystiene residues to resemblelysine, and subjected to trypsin hydrolysis. The resulting peptides were separated by acombination of electrophoresis and paper chromatography and compared to normalhemoglobin. In each case only one peptide differed from the normal hemoglobin peptidemap. The amino acid composition of the affected peptides is shown in the table below.Source of Variant Peptide Amino Acid CompositionArg Asp+AsnGlu+GlnPro Gly Ala Val