[2018-1 학기 ] 토요과학공개강좌 금속이단백질을만났을때 2018. 04. 14. 토요일 서울대학교화학부송윤주
개요 I. 금속이란? II. 단백질이란? III. 금속과단백질이만났을때
환원주의 (Reductionism) 철학에서복잡하고높은단계의사상이나개념을하위단계의요소로세분화하여명확하게정의할수있다고주장하는견해 I am a chemist! 르네데카르트 (René Descartes)
원자, Atom H 2 O H hydrogen O oxygen 원자 : 물질을구성하는기본입자. 예 ) H, O 분자 : 여러원자의화학적결합으로이루어진입자. 예 ) H 2 O
분자, Molecule 물 (H 2 O) 분자 6.02 X 10 23 개의질량 : 18 g 50 kg 사람이 100% 물로만이루어져있다면, 50X1000/(18g)X 6.02 X10 23 = 1.7 X10 27 = 1700000000000000000000000000 개의물분자로구성 Avogadro s number: 6.02 X 10 23
Every atom you possess has almost certainly passed through several stars and been part of millions of organisms on its way to becoming you. We are each so atomically numberous and so vigorously recycled at death that a significant number of our atoms-up to a billion for each of us, it has been suggested-probably once belonged to Shakespeare. A billion more each came from Buddha and Genghis Khan and Beethoven, and any other historical figure you care to name. William McGuire "Bill" Bryson 거의모든것의역사 " 에서 A billion (10 9 ) atoms are not enough to make even a brain cell. But it is still pretty cool!
원자와분자의크기 http://www.basicknowledge101.com/categories/nano.html
The World's Smallest Movie IBM: Published on Apr 30, 2013 Carbon monoxide (CO) Scanning tunneling microscope (STM) - Magnetic properties of atoms on the surfaces: how small can you make the magnetic smaller and use it for data storage. - 100 million times magnified: If the atom is the size of orange, then, the orange is the size of the Planet Earth.
Periodic Table ( 주기율표 ) - Updated on 28 November 2016 - Includes the recently added elements 113, 115, 117, and 118 with their names and symbols - Named after a place or geographical region, or a scientist. - Nh: Nihon which is one of the two ways to say Japan in Japanese; Mc: Moscovium is in recognition of the Moscow region; Ts: Tennessee region of the United States; Og: Professor Yuri Oganessian
화학학문분야의전통적분류 유기화학 (Organic Chemistry) : 유기 ( 탄소원자 ) 화합물의구조나특성, 제법및응용등을연구 무기화학 (Inorganic Chemistry) : 화학에서유기화학의여집합의개념으로출발 물리화학 (Physical Chemistry) 분석화학 (Analytical Chemistry) 생화학 (Biochemistry) * 현재는분류가모호한경우도많음 : 생물리, 생유기, 생무기, 금속유기등등
유기농무기농? 비료의성분은질소, 인산, 칼륨, 황, 칼슘, 마그네슘등으로구성되어있으며, 식물이많은양을필요로하여부족되기쉽기때문 농약과비료등의합성화학물질을사용하지않고재배한경우 그렇다면 무기 " 는항상안좋은것일까요?
광합성 O 2 자연과우리생활에있는다양한금속 ( 이온들 ) 기름을분해하는박테리아 비타민영양제
원자의구성 양성자 (proton) 중성자 (neutron) 전자 (electron) : 원자간의전자의교환이나공유가화학반응 / 결합을일으킴 양성자 + 중성자 ( 핵 : nucleus)
금속원자의특성 전자를잃거나얻는반응, 즉산화, 환원반응을할수있다. 전자를매개로결합된금속결합을할수있다. 전자기성을가지는경우가많다.
Periodic Table ( 주기율표 ) 전자주고, 양이온이되기쉬움 전자를주거나받거나할수있음 (-1, -2 등의음이온이나 +1, +2, +3, +4 등의양이온형성 ). 전자받고, 음이온이되기쉬움
I. 중간정리 모든물질은원자로구성되어있다. 원자간의화학결합에의해서분자가만들어진다. 다양한원자들은주기적인성질을가지고있다 ( 주기율표 ). 그중에서금속원자들은산화, 환원반응을잘하며, 전자의주고받는반응을잘한다.
개요 I. 금속이란? II. 단백질이란? III. 금속과단백질이만났을때
단백질이란? Atom ( 원자 ) 아미노산 - 20 개의아미노산 - 다양한크기및화학적특성을가짐 - 아미노산의조합으로단백질이구성됨
단백질이란? Atom ( 원자 ) 아미노산 펩타이드
2 차구조 알파나선 베타병풍
단백질이란? 펩타이드 Atom ( 원자 ) 아미노산 단백질
2017 년 8 월 24 일기준 133,093 개의단백질구조가밝혀짐
133,093 개의단백질구조가밝혀짐 단백질의종류 Escherichia coli ( 대장균 ) Length: 2.0 μm 2 million proteins per cell ~1800 known proteins so far. Human cell length: 100 µm 1-3 billion proteins per cell 19,467 known proteins so far.
Central Dogma DNA RNA 단백질 transcription translation 전사번역
인간게놈프로젝트 (1990 2003) DNA 시퀀싱 Humans have only around 20,000, compared to earlier estimates of 100,000. What happens after the Human Genome Project? http://www.sciencemuseum.org.uk The focus now is on understanding how these genes are regulated and what role they play.
Bioinformatics, Metagenomics, Interactome Nature Review Microbiology, 2005, 3, 470
단백질접힘 (Protein Folding) - Inter or intra-molecular hydrogen bonding - Hydrophobic interactions - Chaperones Trends in Biochemical Sciences, 2000, 25, 331
단백질접힘 (Protein Folding) Nature Education, 2010, 3, 28 Nature Reviews Molecular Cell Biology, 2005, 6, 971
원자수준에서단백질의구조를알기위한방법 1) X- 선결정법 2) 핵자기공명법 (NMR) 3) cryo-em ( 극저온전자현미경 )
X- 선결정법 (X-ray Crystallography) - 현재까지 29 명의과학자가 X- 선결정법관련연구로노벨상을수상했음.
Int. J. Mol. Sci. 2013, 14(6), 11643-11691; doi:10.3390/ijms140611643
space earth space earth International Space Station Research (NASA)
핵자기공명분광법 (NMR) - 현재까지 8 명의과학자가 NMR 관련연구로노벨상을수상했음.
핵자기공명분광법 (NMR) 을이용한단백질의구조연구
Nobel prize in chemistry awarded to Jacques Dubochet, Joachim Frank and Richard Henderson for method to visualize biomolecules, cryo-electron microscopy (2017).
극저온전자현미경 (cryo-em)
단백질의기능과상호작용
효소 (Enzyme): 생체촉매 (Catalyst) Active Site 활성화부위
The Power of Enzymes ADC: arginine decarboxylase; ODC: orotidine 5 -phosphate decarboxylase STN: staphylococcal nuclease; GLU: sweet potato β-amylase FUM: fumarase; MAN: mandelate racemase PEP: carboxypeptidase B; CDA: E. coli cytidine deaminase KSI: ketosteroid isomerase; CMU: chorismate mutase CAN: carbonic anhydrase Acc. Chem. Res. 2001, 34, 938-945
Dioxygen Transfer Pathway in Toluene/o-Xylene Monooxygenase (ToMO) O 2 ToMOH hydroxylase 2H + + 2e - + O 2 + RH ROH + H 2 O The diiron active center of ToMOH lie adjacent to hydrophobic pockets, buried approximately 12 Å beneath the protein surface.
Dioxygen Transfer Pathway in Toluene/o-Xylene Monooxygenase (ToMO) O 2 ToMOH hydroxylase The diiron active center of ToMOH lie adjacent to hydrophobic pockets, buried approximately 12 Å beneath the protein surface.
Hydrophobic Pockets; Candidates for O 2 Transfer Pathway Several hydrophobic sites (Cavities 1-3, Channel, and Pore) are found in ToMOH. What is the O 2 transfer pathway to the diiron active sites? *T201S mutation to generate an intermediate that forms with the rate constants, which are dependent on the dioxygen concentrations. J. Am. Chem. Soc. 2009, 131, 6074-6075 J. Am. Chem. Soc. 2010, 132, 13582 13585
Cavities: Selective Dioxygen Transfer Pathway O 2 Hydroxylase Only (PDB 2INC) Dioxygen Transfer is Gated by the Transient opening/closing motions via conformational changes Proc. Natl. Acad. Sci., 2011, 108, 14795-14800 Complex structure of hydroxylase and regulatory protein in methane monooxygenase (4GAM) Nature, 2013, 494, 380-385
II. 중간정리 단백질은아미노산간의결합된펩타이드로구성되어있다. 단백질의구조와종류는매우다양하다. 단백질을이루는아미노산의서열은 DNA 를거쳐 RNA 를통해서발현된다. 단백질의접힘현상은매우중요하며, 여러가지물리 / 화학작용에의해이루어진다. 단백질의구조와기능을알기위한연구가활발히진행되고있다.
개요 I. 금속이란? II. 단백질이란? III. 금속과단백질이만났을때
금속이온과주로결합하는아미노산 CO 2 -, S-, O- 처럼음이온을형성하기쉬운작용기를가지는아미노산이금속이온과주로결합함. Zinc Finger motif Cysteine Histidine Cysteine Histidine
금속단백질 금속 (metal) + 단백질 (protein) = 금속단백질 (metalloprotein) Nature 2009, 460, 823-830 - 약 30% 의단백질은금속이온을가지고발견됨. 금속단백질은금속, 단백질연구의역사와함께함!
금속단백질 : 금속이온의선택성과항상성 Science, 2001, 292, 2488 Chem. Rev, 2009, 109, 4644
Zn 첫번째로서열분석이된단백질 : 인슐린 Zn Frederick Sanger (1918-2013) Nobel Prize in Chemistry (1958, 1980) DNA 서열분석 Dorothy Hodgkin (1910-1994) Nobel Prize in Chemistry (1964) X- 선결정구조분석 인슐린 : 혈액속의포도당의양을일정하게유지
Metals in Protein-Protein Interface Annu. Rev. Biophysics, 2014, 43, 409
Metal-Mediated Protein Self-Assembly + Metal Ions
Zn Metal-Mediated Protein Self-Assembly 4X +4 Zn cytochrome cb 562 J. Am. Chem. Soc. 2010, 132, 8610-8617 Nat. Chem. 2012, 4, 375-382
Zn 아연, Zinc (Zn) M-OH 2 H 2 O Ca(OH 2 ) Zn(OH 2 ) [Fe(OH 2 ) 2 ] 3+ pk a 14 13.4 10.0 3 Zn(OH 2 ) in CA 6.8 insulin carbonic anhydrase 탄산탈수효소 CO 2 + H 2 O H 2 CO 3 H + + HCO 3 - one of the fastest enzymes (turnover rate = ~10 4-10 6 s -1 ) H 2 O H + + OH - K a = [H + ][OH - ]/[H 2 O] = ~10-14 (ph 7) Acc. Chem. Res. 1996, 29, 331-339
Zn 아연, Zinc (Zn) insulin carbonic anhydrase 탄산탈수효소 CO 2 + H 2 O H 2 CO 3 H + + HCO 3 - one of the fastest enzymes (turnover rate = ~10 4-10 6 s -1 ) zinc finger motif zinc finger nucleases
카스 9 분해효소 (Cas9 nuclease): 유전자가위 Zinc finger domain 이아닌 grna 가특정서열을인식함 Prof. Jennifer Doudna (UC Berkeley) Protospacer adjacent motif Prof. Feng Zhang (MIT) 김진수교수 (IBS, 서울대화학부 )
Fe 첫번째로 3 차구조가밝혀진단백질 : 철단백질 Hemoglobin and Myoglobin (1962 Noble prize in chemistry) Max Perutz (1014-2002) Fe 포르피린 (Porphyrin): Heme John Kendrew (1917-1997)
Fe Hemoglobin: O 2 Transport Protein 길이 : 7-8 μm 1 개당단백질약 2 억 8 천만개를포함 : 문제 : 적혈구 1 개는몇개의산소분자를운반할수있을까요? 정답 : 11 억 2 천만개 Sickle-cell disease 낫적혈구병, 겸상적혈구병
Fe 산화효소, Cytochrome P450 Monooxygenase R-H Fe III R-H e - Cys Fe II S O 2 O O- R-H FeIII H 2 O Cys S Cys S e - R-H H H O FeIII O 2- O R-H Fe III Cys S R-OH Drug metabolism Detoxification R-H Cys O Fe IV S R-H + H 2 O H + Cys O OH R-H Fe III S Cys S H+
Fe 메탄산화효소, Methane Monooxygenase 2H + + 2e + O 2 + CH 4 CH 3 OH + H 2 O
셰일가스 (Shale gas): 천연가스의일종으로확인된매장량은석유매장량의총열량과비슷하며, 메탄가스등의혼합물임. 메탄가스 : 온난화의주요원인중에하나임. 이와같은메탄가스를산화시켜메탄올로만드는연구등이활발히진행중임!
Cu 메탄산화효소, Methane Monooxygenase 박테리아의생장환경에따라서철대신구리로메탄산화효소를만들기도함.
Cu Hemocyanin: O 2 Transport Protein 연체동물 (mollusks) O 2 2- + O 2 Cu +1, Cu +1 Cu +2, Cu +2
Co 코발트, Cobalt (Co) Vitamin B 12 = cobalamin Co(I) Co(III)-CH 3
The Nobel Prize in Chemistry 1964 She has determined the structure of penicillin in 1946 and, in 1956, also the structure of vitamin B12, which has the most complex structure of all vitamins. In 1969, she determined the structure of insulin. Dorothy Crowfoot Hodgkin (1910-1994) Determination of X-ray structures of important biochemical substances" penicillin Vitamin B 12 = cobalamin Insulin-took 34 yrs!
PSII: photosystem II 광합성, Photosynthesis
Mn Photosystem II: Oxygen Evolving Complex 2H 2 O 4H + + 4e - + O 2
질소고정화반응 (Nitrogen Fixation) 19 세기 : 인구의급증, 식량문제의해결필요성대두 비료 : 질소화합물 + 칼륨 + 인화합물등 질소화합물을만드는방법, 즉질소고정화반응에대한연구가필요해짐
질소고정화반응 (Nitrogen Fixation) Kristian Birkeland (1867 1917) Wilhelm Ostwald (1853 1932) Nobel Prize in Chemistry in 1909 Typically at 2000-3000 o C 전기를이용한질소산화
Fe 하버 - 보쉬 (Haber-Bosch) 법 Fritz Haber (1868-1934) Nobel Prize in Chemistry (1918) Carl Bosch (1874-1940) 3H₂(g)+N₂(g) 2NH₃(g) 2500 개의촉매물질을사용해서 6500 번의실험을했으며, 약 10,000 번의실험의결과임! Fe catalyst
Fe 하버 - 보쉬 (Haber-Bosch) 법 https://pubs.acs.org/cen/coverstory/86/8633cover3box2.html Fritz Haber (1868-1934) Nobel Prize in Chemistry (1918) World War I poison gas gas warfare
Mo/V 질소고정효소 (Nitrogenase) Fe FeS Cluster Mo Cyanobacteria (~5 μm size) N 2 + 8H + + 8 e - + 16 ATP 2NH 3 + H 2 + 16 ADP + 16 Pi 또는 V
Mo/V 질소고정효소 (Nitrogenase) Fe Nature, 2013, 501, 84 Nitrogenase in 23 o C and 1 atm vs Haber-Bosch catalysts in 450 o C and 300 bar
III. 마지막정리 Fe Mo/V Zn Mn Co Cu
금속단백질및효소에대한연구 미지의유전자와단백질 Chem. Rev., 2017, ASAP Bioinorganic Chemistry Lab at SNU
What I cannot create, I do not understand. -Richard Feynman (1918-988) Although I can create, I do not understand. -Anonymous
Design of Metal/Protein-Based Biocatalysts/Biomaterials Proteins + Metal Ions/Metal Cofactors Diverse structures with Rigidity and flexibility Biocompatible Genetic engineering Selective expression in the cellular space Evolvability Selective interactions with other biomolecules Directionality (Coordination Geometry) Lewis acidity Nucleophilicity/Electrophilicity Multiple oxidation states Responsiveness to the external stimuli
Design of Metal/Protein-Based Biocatalysts/Biomaterials