This document provides an overview for a molecular murder mystery activity where students will work in groups to identify substances bound to the active site of cytochrome c oxidase using 3D protein structures downloaded from an online source. Background information is given on the protein including its normal function of reducing oxygen to water. Students will develop a mystery story and use online resources to deduce what is bound to different protein structures. The goal is to help students learn while practicing skills for identifying elements and active sites in proteins.

1. 11 © 2009 PerkinElmer© 2009 PerkinElmer© 2009 PerkinElmer© 2013 Digital World Biology
Molecular Murder Mysteries
Sandra Porter, Ph.D. @digitalbio,
sandra@digitalworldbiology.com

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Thanks to…
www.bio-link.org
Biotech-careers.org
NWABR.org
National Science Foundation
Bio-ITEST, DRL 0833779
National Science Foundation
Bio-Link DUE 0903317

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Overview
Practice
Divide into groups – up to 7
Solve mysteries
Present results
Schedule

4. 44 Not just for barcoding!
Cytochrome C Oxidase
A B
C D

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Gene name Protein name Gene location 1OCC chain
MT-COI cytochrome c oxidase subunit I Mitochondrion A
MT-CO2 cytochrome c oxidase subunit II Mitochondrion B
MT-CO3 cytochrome c oxidase III Mitochondrion C
COX4I1 cytochrome c oxidase subunit IV isoform 1 Chromosome 16 D
COX4I2 cytochrome c oxidase subunit IV isoform 2 (lung) Chromosome 20 D
COX5A cytochrome c oxidase subunit Va Chromosome 15 E
COX5B cytochrome c oxidase subunit Vb Chromosome 2 F
COX6A1 cytochrome c oxidase subunit VIa polypeptide 1 Chromosome 12 G
COX6A2 cytochrome c oxidase subunit VIa polypeptide 2 Chromosome 16 G
COX6B1 cytochrome c oxidase subunit VIb polypeptide 1 Chromosome 19 H
COX6B2 cytochrome c oxidase subunit VIb polypeptide 2 (testis) Chromosome 19 H
COX6C cytochrome c oxidase subunit VIc Chromosome 8 I
COX7A1 cytochrome c oxidase subunit VIIa polypeptide 1 (muscle) Chromosome 19 J
COX7A2 cytochrome c oxidase subunit VIIa polypeptide 2 (liver) Chromosome 6 J
COX7B cytochrome c oxidase subunit VIIb Chromosome X K
COX7B2 cytochrome c oxidase subunit VIIb2 Chromosome 4 K
COX7C cytochrome c oxidase subunit VIIc Chromosome 5 L
COX8A cytochrome c oxidase subunit VIIIA Chromosome 11 M
COX8C cytochrome c oxidase subunit VIIIC Chromosome 14 M
Not just for barcoding!
Cytochrome C Oxidase

6. 66 Not just for barcoding!
Cytochrome C Oxidase
O2
H2O

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Goal – to identify the substance bound to the active site
Come up with a mystery story to explain what happened
Prerequisite knowledge
 Identify 3 key elements (oxygen, nitrogen, carbon)
 Use Wikipedia
 Be familiar with the concept of an active site
 Use Cn3D
Molecular Murder Mysteries

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Go to figshare.com
Search for cytochrome C oxidase – see lots of structures
 Download 1OCC.cn3 – cytochrome C oxidase
Look at features of structure
Practice with Cn3D
Figure out colors for elements
Molecular Murder Mysteries

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Molecular Murder Mysteries

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Positively charged amino acid
Molecular Murder Mysteries

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Molecular Murder Mysteries
Group Structure What is bound to the active site?
Control 1OCC_3ABM_anno1.cn3 Oxygen – normal function of protein reduces
O2 to H2O
A 1OCC_1OCO
B 1OCC_1OCZ
C 1OCC_3AG1
D 1OCC_3AG2
E 1OCC_3AG3
F 1OCC_3AG4
G 1OCC_3ABK