NEED HELP PLEASE. CAN YOU PLEASE DO IT ALL NOT JUST ANSWER ONE.

MY ANIMALS ARE: HUMAN, KANGAROO, RHESUS MONKEY, BULLFROG, LAMPREY, SNAPPING TURTLE, TUNA, AND EARTHWORM

Step 3: Cytochrome c Analysis

Scientists have found that almost all living organisms have a gene that codes for a protein called Cytochrome c. This chart lists the amino acids found in the Cytochrome c protein of some of the organisms on your cladogram.

Note: not all the organisms you used will be in the chart; as such, you can focus this analysis on the animals that are in the chart. If you only chose three animals that are in the chart, you should probably extend your amino acid analysis to include a couple animals that arenât on your cladogram.

You will use the data provided in this chart to compare and analyze the amino acid sequences for Cytochrome c among these organisms. Be sure that your comparison considers the entire amino acid sequence, through amino acid 112, and not just the first lines of the chart. Once you have compared the sequences, you will write a discussion about your findings.

Amino Acid Sequences in Cytochome-C Proteins

1-30

Amino Acid Position Number

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

25

26

27

28

29

30

Human, Chimpanzee

-

G

D

V

E

K

G

K

I

F

I

M

K

C

S

Q

C

H

T

V

E

K

Rhesus Monkey

-

G

D

V

E

K

G

K

I

F

I

M

K

C

S

Q

C

H

T

V

E

K

Horse

-

G

D

V

E

K

G

K

I

F

V

Q

K

C

A

Q

C

H

T

V

E

K

Pig, Cow, Sheep

-

G

D

V

E

K

G

K

I

F

V

Q

K

C

A

Q

C

H

T

V

E

K

Dog

-

G

D

V

E

K

G

K

I

F

V

Q

K

C

A

Q

C

H

T

V

E

K

Gray Whale

-

G

D

V

E

K

G

K

I

F

V

Q

K

C

A

Q

C

H

T

V

E

K

Rabbit

-

G

D

V

E

K

G

K

I

F

V

Q

K

C

A

Q

C

H

T

V

E

K

Kangaroo

-

G

D

V

E

K

G

K

I

F

V

Q

K

C

A

Q

C

H

T

V

E

K

Penguin

-

G

D

I

E

K

G

K

I

F

V

Q

K

C

S

O

C

H

T

V

E

K

Snapping Turtle

-

G

D

V

E

K

G

K

I

F

V

Q

K

C

A

Q

C

H

T

V

E

K

Bullfrog

-

G

D

V

E

K

G

K

I

F

V

Q

K

C

A

Q

C

H

T

C

E

K

Tuna

-

G

D

V

A

K

G

K

T

F

V

Q

K

C

A

Q

C

H

T

V

E

N

31-60

Amino Acid Position Number

31

32

33

34

35

36

37

38

39

40

41

42

43

44

45

46

47

48

49

50

51

52

53

54

55

56

57

58

59

60

Human, Chimpanzee

G

K

H

K

T

G

P

N

L

H

G

L

F

G

R

K

T

G

Q

A

P

G

Y

S

Y

T

A

N

Rhesus Monkey

G

K

H

K

T

G

P

N

L

H

G

L

F

G

R

K

T

G

Q

A

P

G

Y

S

Y

T

A

N

Horse

G

K

H

K

T

G

P

N

L

H

G

L

F

G

R

K

T

G

Q

A

P

G

F

T

Y

T

D

A

N

Pig, Cow, Sheep

G

K

H

K

T

G

P

N

L

H

G

L

F

G

R

K

T

G

Q

A

P

G

F

S

Y

T

D

A

N

Dog

G

K

H

K

T

G

P

N

L

H

G

L

F

G

R

K

T

G

Q

A

P

G

F

S

Y

T

D

A

N

Gray Whale

G

K

H

K

T

G

P

N

L

H

G

L

F

G

R

K

T

G

Q

A

V

G

F

S

Y

T

D

A

N

Rabbit

G

K

H

K

T

G

P

N

L

H

G

L

F

G

R

K

T

G

Q

A

V

G

F

S

Y

T

D

A

N

Kangaroo

G

K

H

K

T

G

P

N

L

N

G

I

F

G

R

K

T

G

Q

A

P

G

F

T

Y

T

D

A

N

Penguin

G

K

H

K

T

G

P

N

L

H

G

I

F

G

R

K

T

G

Q

A

E

G

F

S

Y

T

D

A

N

Snapping Turtle

G

K

H

K

T

G

P

N

L

N

G

L

I

G

R

K

T

G

Q

A

E

G

F

S

Y

T

E

A

N

Rattlesnake

G

K

H

K

T

G

P

N

L

H

G

L

F

G

R

K

T

G

Q

A

V

G

Y

S

Y

T

A

N

Bullfrog

G

K

H

K

V

G

P

N

L

Y

G

L

I

G

R

K

T

G

Q

A

G

F

S

Y

T

D

A

N

Tuna

G

K

H

K

V

G

P

N

L

W

G

L

F

G

R

K

T

G

Q

A

E

G

Y

S

Y

T

D

A

N

61-90

Amino Acid Position Number

61

62

63

64

65

66

67

38

69

70

71

72

73

74

75

76

77

78

79

80

81

82

83

84

85

86

87

88

89

90

Human, Chimpanzee

K

N

K

G

I

W

G

E

D

T

L

M

E

Y

L

E

N

P

K

Y

I

P

G

T

K

M

I

F

Rhesus Monkey

K

N

K

G

I

T

W

G

E

D

T

L

M

E

Y

L

E

N

P

K

Y

I

P

G

T

K

M

I

F

Horse

K

N

K

G

I

T

W

K

E

T

L

M

E

Y

L

E

N

P

K

Y

I

P

G

T

K

M

I

F

Pig, Cow, Sheep

K

N

K

G

I

T

W

G

E

T

L

M

E

Y

L

E

N

P

K

Y

I

P

G

T

K

M

I

F

Dog

K

N

K

G

I

T

W

G

E

T

L

M

E

Y

L

E

N

P

K

Y

I

P

G

T

K

M

I

F

Gray Whale

K

N

K

G

I

T

W

G

E

T

L

M

E

Y

L

E

N

P

K

Y

I

P

G

T

K

M

I

F

Rabbit

K

N

K

G

I

T

W

G

E

D

T

L

M

E

Y

L

E

N

P

K

Y

I

P

G

T

K

M

I

F

Kangaroo

K

N

K

G

I

W

G

E

D

T

L

M

E

Y

L

E

N

P

K

Y

I

P

G

T

K

M

I

F

Penguin

K

N

K

G

I

T

W

G

E

D

T

L

M

E

Y

L

E

N

P

K

Y

I

P

G

T

K

M

I

F

Snapping Turtle

K

N

K

G

I

T

W

G

E

T

L

M

E

Y

L

E

N

P

K

Y

I

P

G

T

K

M

I

F

Rattlesnake

K

N

K

G

I

W

G

D

T

L

M

E

Y

L

E

N

P

K

Y

I

P

G

T

K

M

V

F

Bullfrog

K

N

K

G

I

T

W

G

E

D

T

L

M

E

Y

L

E

N

P

K

Y

I

P

G

T

K

M

I

F

Tuna

K

S

K

G

I

V

W

N

D

T

L

M

E

Y

L

E

N

P

K

Y

I

P

G

T

K

M

I

F

91-112

Amino Acid Position Number

91

92

93

94

95

96

97

98

99

100

101

102

103

104

105

106

107

108

109

110

111

112

Human, Chimpanzee

V

G

I

K

E

R

A

D

L

I

A

Y

L

K

A

T

N

E

Rhesus Monkey

V

G

I

K

E

R

A

D

L

I

A

Y

L

K

A

T

N

E

Horse

A

G

I

K

T

E

R

E

D

L

I

A

Y

L

K

A

T

N

E

Common Zebra

A

G

I

K

T

E

R

E

D

L

I

A

Y

L

K

A

T

N

E

Pig, Cow, Sheep

A

G

I

K

G

E

R

E

D

L

I

A

Y

L

K

A

T

N

E

Dog

A

G

I

K

T

G

E

R

A

D

L

I

A

Y

L

K

A

T

K

E

Gray Whale

A

G

I

K

G

E

R

A

D

L

I

A

Y

L

K

A

T

N

E

Rabbit

A

G

I

K

D

E

R

A

D

L

I

A

Y

L

K

A

T

N

E

Kangaroo

A

G

I

K

G

E

R

A

D

L

I

A

Y

L

K

A

T

N

E

Penguin

A

G

I

K

S

E

R

A

D

L

I

A

Y

L

K

D

A

T

S

K

Snapping Turtle

A

G

I

K

A

E

R

A

D

L

I

A

Y

L

K

D

A

T

S

K

Rattlesnake

T

G

L

K

E

R

T

D

L

I

A

Y

L

K

E

A

T

A

K

Bullfrog

A

G

I

K

G

E

R

Q

D

L

I

A

Y

L

K

S

A

C

S

K

Tuna

A

G

I

K

G

E

R

Q

D

L

V

A

Y

L

K

S

A

T

S

-

More information:

Cytochrome c is a protein used in cellular respiration by most eukaryotes, which is why it's a very common protein to use for comparisons. You don't need to know anything about cellular respiration or the protein itself to do this analysis; just remember that a protein is a specific chain of amino acids.

Which amino acids are found, and the order in which they're found (their sequence), determine the shape, structure, and function of the protein. Also remember that an amino acid sequence is directly determined by the DNA sequence, so similarities in one also indicate similarities in the other.

Please note that the entire sequence of 112 amino acids represents one protein, and this sequence data is all one chart, not four. As such, your analysis should consider the sequence as a whole, and not amino acids 1 â 30, then amino acids 31 â 60, etc.

Be careful not to read too much into the differences you find. Since this analysis only looks at one protein, you will not be able to connect differences here to specific differences in traits between organisms. In other words, it might be that all animals with a placenta have a âVâ at a particular location, while animals without a placenta have either a âCâ or a âK.â That similarity helps us confirm that those animals with a placenta are more closely related to each other than to the others, but the âVâ does not code for the placenta, nor is it related to that particular trait at all.

How to Analyze the Data

While you analyze the data that you are given to identify similarities and differences, be sure to use specific data to draw your comparisons, hypotheses, and discussions from. It is especially helpful to quantitatively compare data. A good way to do this, or at least to start, is to pick one species as a starting point or âbaselineâ and then compare the amount of differences between that and each other species. Be careful, though, about the conclusions you draw â if species B and C each have 5 differences from species A, then they could have anywhere from 0 to 10 differences with each other!

Once youâve compared each animal to a baseline animal, you should also compare other pairs of species so that you can discuss their specific relationships. If you only have a few animals with data to analyze in part C, you could simply make this comparison for every pair. If you have 6 or 7 animals, then you could pick just a few pairs to compare.

There are other legitimate ways to form quantitative data â for instance, you could focus on specific locations where most animals have the same amino acid, but some are different. These types of analysis tend to be harder to interpret, though. If you choose to use them, I suggest that you still complete at least some of the above types of analysis as well.

The discussion topics that I'm looking for are:

Use the chart to compare the amino acid sequences for the organisms. Do this in a way that lets you obtain quantitative (numerical) data; see above for suggestions.

Hypothesize about how closely related the different organisms are, based on the amino acid data in the chart.

In particular, focus on organisms that are also found on your phylogenetic tree, but you may choose to discuss others, too. That would be especially helpful if you used only three or four of the organisms that are also in the chart, or if one or more organisms that you did not include in your tree jump out at you as being especially similar or especially different from the ones you did include.

This does not need to be in the form of a formal hypothesis; that is, you do not need to put this in âif/then/becauseâ form.

Because âhow closely relatedâ can be interpreted in many ways, itâs often helpful to put this in relative terms: âAnimal D is the closest relative to Animal A.â âAnimals C and B are more closely related to each other than either one is to Animal D.â

Discuss how this analysis compares to the relationships that were shown on your phylogenetic tree.

To start, does the Cytochrome c data agree or disagree with the relationships shown on the tree?

Remember that "discuss" means more than simply identifying whether the relationships are the same or different as what is shown. You can also suggest why they're likely the same, or what possible differences could imply, if anything. See the note at the end of âMore Informationâ above â donât read TOO MUCH into any one piece of data!

If your amino acid analysis included animals that werenât on your cladogram, you could use your amino acid data to speculate where they likely âfitâ on the cladogram.

The phrase âcommon ancestorâ should show up somewhere in this discussion.

Please be aware that Step 3 should be written as a short essay, not a list or set of questions and answers. You may include a chart or table for the quantitative data you identified, but the key findings should also be written in sentence form. Once youâve finished writing this, please proofread for spelling, grammar, and writing clarity.

Step 3 should be a sizeable portion of this portfolio. I expect that your analysis should be about 250 â 400 words long in order to thoroughly analyze the data and discuss the questions.

ambermuskrat111

Enzyme Dysfunction in Disease (30 pts)

Protein kinases are key regulators of cellular physiology and, consequently, their dysfunction is associated with many diseases. Conversely, mutations and other defects sometimes help to illuminate gene function. Continuing with the exploration of the PI3K/AKT pathway, this exercise will seek to illuminate the role of certain residues and motifs in molecular functioning of AKT.

(1) Diseases associated with AKT1 mutations were identified in the first exercise. Following the same procedure and PUBMED searches, identify diseases associated mutations of AKT2 and AKT3 (some relevant papers are provided below).

(2) Through literature search or the references below, generate a table of disease-associated mutations of the above genes.

(4) Generate a hypothesis on the role of the PI3K/Akt in cancer or any other disease.

(5) Make predictions based on experiments that can be conducted in cell lines.

(4) Conduct sequence alignments of these proteins by selecting homologues from divergent species and identify the most highly conserved residues and motifs.

(5) Download the structure of AKT with and without ligands from the PDB and propose the consequences of the above mutations in protein function.

(6) Propose some experiments to test the predictions.

(7) Highlight three of the most highly conserved motifs on the protein structure and comment on their possible role in AKT function.

1. Revival of the abandoned therapeutic wortmannin by nanoparticle drug delivery.

Karve S, Werner ME, Sukumar R, Cummings ND, Copp JA, Wang EC, Li C, Sethi M, Chen RC, Pacold ME, Wang AZ. Proc Natl Acad Sci U S A. 2012 May 22;109(21):8230-5. doi: 10.1073/pnas.1120508109. Epub 2012 Apr 30. PMID: 22547809 Free PMC Article

2. Phase I clinical, pharmacokinetic, and pharmacodynamic study of the Akt-inhibitor triciribine phosphate monohydrate in patients with advanced hematologic malignancies.

Sampath D, Malik A, Plunkett W, Nowak B, Williams B, Burton M, Verstovsek S, Faderl S, Garcia-Manero G, List AF, Sebti S, Kantarjian HM, Ravandi F, Lancet JE. Leuk Res. 2013 Nov;37(11):1461-7. doi: 10.1016/j.leukres.2013.07.034. Epub 2013 Aug 6.PMID: 23993427

The Mechanism of ATP-Dependent Allosteric Protection of Akt Kinase Phosphorylation.

Lu S, Deng R, Jiang H, Song H, Li S, Shen Q, Huang W, Nussinov R, Yu J, Zhang J.

Structure. 2015 Sep 1;23(9):1725-34. doi: 10.1016/j.str.2015.06.027. Epub 2015 Aug 6.

PMID:26256536

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Select item 262867482.

Alternative activation mechanisms of Protein Kinase B trigger distinct downstream signaling responses.

Balzano D, Fawal MA, Velazquez JV, Santiveri CM, Yang J, Pastor J, Campos-Olivas R, Djouder N, Lietha D.

J Biol Chem. 2015 Aug 18. pii: jbc.M115.651570. [Epub ahead of print]

PMID:26286748

Free Article

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Mutant AKT1-E17K is oncogenic in lung epithelial cells.

De Marco C, Malanga D, Rinaldo N, De Vita F, Scrima M, Lovisa S, Fabris L, Carriero MV, Franco R, Rizzuto A, Baldassarre G, Viglietto G.

Oncotarget. 2015 May 25. [Epub ahead of print]

PMID:

26053093

Free Article

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Activating AKT2 mutation: hypoinsulinemichypoketotic hypoglycemia.

Arya VB, Flanagan SE, Schober E, Rami-Merhar B, Ellard S, Hussain K.

J ClinEndocrinolMetab. 2014 Feb;99(2):391-4. doi: 10.1210/jc.2013-3228. Epub 2013 Nov 27.

PMID:

24285683

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AGC protein kinases: from structural mechanism of regulation to allosteric drug development for the treatment of human diseases.

Arencibia JM, Pastor-Flores D, Bauer AF, Schulze JO, Biondi RM.

BiochimBiophysActa. 2013 Jul;1834(7):1302-21. doi: 10.1016/j.bbapap.2013.03.010. Epub 2013 Mar 21. Review.

PMID:

23524293

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Resistance of Akt kinases to dephosphorylation through ATP-dependent conformational plasticity.

Chan TO, Zhang J, Rodeck U, Pascal JM, Armen RS, Spring M, Dumitru CD, Myers V, Li X, Cheung JY, Feldman AM.

Proc Natl AcadSci U S A. 2011 Nov 15;108(46):E1120-7. doi: 10.1073/pnas.1109879108. Epub 2011 Oct 26. PMID: 22031698

The nuts and bolts of AGC protein kinases. Pearce LR, Komander D, Alessi DR. Nat Rev Mol Cell Biol. 2010 Jan;11(1):9-22. doi: 10.1038/nrm2822. Review.

PMID: 20027184

Somatic mutations affect key pathways in lung adenocarcinoma.

Ding L, Getz G, Wheeler DA, Mardis ER, McLellan MD, Cibulskis K, Sougnez C, Greulich H, Muzny DM, Morgan MB, Fulton L, Fulton RS, Zhang Q, Wendl MC, Lawrence MS, Larson DE, Chen K, Dooling DJ, Sabo A, Hawes AC, Shen H, Jhangiani SN, Lewis LR, Hall O, Zhu Y, Mathew T, Ren Y, Yao J, Scherer SE, Clerc K, Metcalf GA, Ng B, Milosavljevic A, Gonzalez-Garay ML, Osborne JR, Meyer R, Shi X, Tang Y, Koboldt DC, Lin L, Abbott R, Miner TL, Pohl C, Fewell G, Haipek C, Schmidt H, Dunford-Shore BH, Kraja A, Crosby SD, Sawyer CS, Vickery T, Sander S, Robinson J, Winckler W, Baldwin J, Chirieac LR, Dutt A, Fennell T, Hanna M, Johnson BE, Onofrio RC, Thomas RK, Tonon G, Weir BA, Zhao X, Ziaugra L, Zody MC, Giordano T, Orringer MB, Roth JA, Spitz MR, Wistuba II, Ozenberger B, Good PJ, Chang AC, Beer DG, Watson MA, Ladanyi M, Broderick S, Yoshizawa A, Travis WD, Pao W, Province MA, Weinstock GM, Varmus HE, Gabriel SB, Lander ES, Gibbs RA, Meyerson M, Wilson RK.

Nature. 2008 Oct 23;455(7216):1069-75. doi: 10.1038/nature07423. PMID: 18948947

Mechanism for activation of the growth factor-activated AGC kinases by turn motif phosphorylation. Hauge C, Antal TL, Hirschberg D, Doehn U, Thorup K, Idrissova L, Hansen K, Jensen ON, JÃ¸rgensen TJ, Biondi RM, FrÃ¶din M. EMBO J. 2007 May 2;26(9):2251-61. Epub 2007 Apr 19. PMID: 17446865

Structure, regulation and function of PKB/AKT--a major therapeutic target.

Hanada M, Feng J, Hemmings BA.

BiochimBiophysActa. 2004 Mar 11;1697(1-2):3-16. Review.

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AKT/PKB and other D3 phosphoinositide-regulated kinases: kinase activation by phosphoinositide-dependent phosphorylation.

Chan TO, Rittenhouse SE, Tsichlis PN Annu Rev Biochem. 1999; 68():965-1014.

tauperaccoon664

CHEM 1C Lecture 10: Lecture 10

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