Alcohol dehydrogenase

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	== 3D Structures of Alcohol dehydrogenase==		== 3D Structures of Alcohol dehydrogenase==
-	''Update May 2012''	+	''Update January 2013''
	===ADH I===		===ADH I===
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	[[3jv7]] – RrADH I – ''Rhodococcus rubber''<br />		[[3jv7]] – RrADH I – ''Rhodococcus rubber''<br />
	[[2vna]] - hADH I catalytic domain - human<br />		[[2vna]] - hADH I catalytic domain - human<br />
-	[[2hcy]] – yADH I – yeast	+	[[2hcy]] – yADH I – yeast<br />
		+	[[4eex]] – LlADH I – ''Lactococcus lactis''<br />
		+	[[4eez]] – LlADH I (mutant)
	''ADH I binary complex''		''ADH I binary complex''
Line 136:		Line 138:
	[[1mc5]] – hADH III χ chain + glutathione + NADH<br />		[[1mc5]] – hADH III χ chain + glutathione + NADH<br />
	[[1ma0]] - hADH III χ chain + dodecanoic acid + NAD<br />		[[1ma0]] - hADH III χ chain + dodecanoic acid + NAD<br />
-	[[3qj5]] - hADH III χ chain + inhibitor + NAD	+	[[3qj5]] - hADH III χ chain + inhibitor + NAD<br />
		+	[[4dl9]], [[4dlb]] – tADH III + NAD – tomato<br />
		+	[[4dla]] – tADH III
	===ADH IV===		===ADH IV===
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	[[1rjw]] – GsADH – ''Geobacillus stearothermophilus''<br />		[[1rjw]] – GsADH – ''Geobacillus stearothermophilus''<br />
	[[1vj0]], [[1vhd]] – TmADH -''Thermotoga maritima''<br />		[[1vj0]], [[1vhd]] – TmADH -''Thermotoga maritima''<br />
-	[[2eer]] – ADH – ''Sulfolobus tokodaii''	+	[[2eer]] – ADH – ''Sulfolobus tokodaii''<br />
		+	[[3uog]] – ADH – ''Sinorhizobium meliloti''
	''ADH binary complex''		''ADH binary complex''
-	[[3l77]] – ADH short-chain + NADP – ''Thermococcus sibiricus''<br />	+	[[3l77]], [[3tn7]] – ADH short-chain + NADP – ''Thermococcus sibiricus''<br />
	[[1h2b]] – ADH + NAD – ''Aeropyrum pernix''<br />		[[1h2b]] – ADH + NAD – ''Aeropyrum pernix''<br />
	[[1f8f]] – Benzyl-ADH + NAD – ''Acinetobacter calcoaceticus''<br />		[[1f8f]] – Benzyl-ADH + NAD – ''Acinetobacter calcoaceticus''<br />
Line 210:		Line 215:
	[[1y9a]] - EhADH – ''Entamoeba histolytica''<br />		[[1y9a]] - EhADH – ''Entamoeba histolytica''<br />
	[[2oui]] – EhADH (mutant) <br />		[[2oui]] – EhADH (mutant) <br />
-	[[1p0c]] – RpADH8 – ''Rana perezi''	+	[[1p0c]] – RpADH8 – ''Rana perezi'' <br />
		+	[[4gac]] - mADH
	''NADP-dependent ADH binary complex''		''NADP-dependent ADH binary complex''

---

Revision as of 13:19, 16 January 2013

spinqualitylabelsall models human alcohol dehydrogenase β3 dimer ternary complex with NAD, iodopyrazole and chloride (green) and Zn+2 (grey) ions, 1htb Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Alcohol dehydrogenase (ADH, EC number 1.1.1.1) is an 80kDa enzyme that catalyzes the 4th step in the metabolism of fructose before glycolysis. In the 4th step, glyceraldehyde is converted to the glycolytic intermediate DHAP by the NADH-dependent, ADH catalyzed reduction to glycerol.^[1] ADH catalyzes the oxidation of primary and secondary alcohols to their corresponding aldehydes and ketones through a mechanism that involves the removal of a hydrogen. For detailed discussion of horse liver alcohol dehydrogenase see Horse Liver Alcohol Dehydrogenase. More detailed discussions in

• Tetrameric alcohol dehydrogenases
  
• Alcohol dehydrogenase from Clostridium beijerinckii
  
• Alcohol dehydrogenase from Entamoeba histolytica
  
• D275P mutant of alcohol dehydrogenase from protozoa Entamoeba histolytica
  
• Contribution of Pro275 to the Thermostability of the Alcohol Dehydrogenases.

Hydroxyacyl-CoA dehydrogenase (HADH) catalyzes the conversion of 3-hydroxyacyl-CoA to 3-oxoacyl-CoA. NAD is the cofactor of HADH activity. HADH oxidates straight-chain 3-hydroxyacyl-CoAs in the β-oxidation pathway of fatty acid metabolism. HADH is classified according to its substrate ads short chain (SHCDH) and long chain HADH. HADH deficiency is a genetic disorder.

For chimeras of alcohol dehydrogenase see

• Chimera of alcohol dehydrogenase by exchange of the cofactor binding domain res 153-294 of T. brockii ADH by E. histolytica ADH
  
• Chimera of alcohol dehydrogenase by exchange of the cofactor binding domain res 153-295 of C. beijerinckii ADH by T. brockii ADH
  
• Chimera of alcohol dehydrogenase by exchange of the cofactor binding domain res 153-295 of T. brockii ADH by C. beijerinckii ADH
  
• Q165E/S254K Double Mutant Chimera of alcohol dehydrogenase by exchange of the cofactor binding domain res 153-295 of T. brockii ADH by C. beijerinckii ADH
  

The of overall Cα backbone of all these chimeras (rmsd 0.45-0.65 Å) with those of the parent enzymes, did not reveal significant structural changes. So, the differences in the thermal stability of the chimeras and the parent enzymes could be caused by relatively small specific changes located at the important points of the NADP⁺-dependent alcohol dehydrogenases. For example see Cα superposition for the X23_(TET) chimera (red) (3fpc) and its parent ADHs (TbADH, colored blue (1ped), and EhADH1, colored lime (1y9a). The RMSDs of the TbADH−EhADH1, TbADH−Χ23_(TET), and EhADH1−Χ23_(TET) were 0.68, 0.56, and 0.48 Å, respectively.

Structure

spinqualitylabelsall models PDB ID 1htb Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

The initial scene () shows an overview of the molecule, allowing for a general look at the tertiary structure of alcohol dehydrogenase (it is complexed with Cl, Pyz, NAD, and Zn). A second scene () shows a close view of the ligand within each subunit. Labels have been placed on NAD, CL, and Zn to clearly establish the structure.

Within alcohol dehydrogenase, site of alcohol dehydrogenase has three important residues, Phe 93, Leu 57, and Leu 116. These three residues work together to bind to the alcohol substrate.^[2]

Zn plays an important role in the catalysis. It funtions by electrostatically stabilizing the oxygen in alcohol during the reaction, which causes the alcohol to be more acidic. At the , Zinc coordinates with Cys 146, Cys 174, and His 67.^[3]

NAD functions as a cosubstrate in the dehydration. NAD binds to numerous residues in a series of beta-alpha-beta folds. shows the domain where NAD binds, and many of the residues with which it interacts are selected. ^[4]

Alcohol dehydrogenase exists as a dimer with a zinc molecule complexed in each of the subunits. It has a SCOP catagory of an alpha and beta protein. At the N-terminal, there is a domain that is all beta; however, the C-Terminal domain is alpha and beta, so the catagory is alpha and beta. The C-Terminal core has 3 layers of alpha/beta/alpha and parallel beta sheets of 6 strands.^[5]

Reaction and Mechanism

In the oxidation mechanism, ADH is momentarily associated with nicontinamide adenine dinucleotide (NAD+), which functions as a cosubstrate. In its reaction, alcohol dehydrogenase uses zinc and NAD to facilitate the reaction. The function of zinc is to position the –OH group on the ethanol in a conformation that allows for the oxidation to occur. NAD then acts as a cosubstrate and performs the oxidation.

^[6] The of alcohol dehydrogenase reaction is as follows: CH3CH2OH + NAD+ -> CH3COH (acetaldehyde) + NADH + H+ (Note: The reaction is actually reversible although the arrow does not show it) ^[7] The step-wise reduction mechanism for ADH is shown on the left. In the mechanism, His 51 is deprotonated and activated by a base catalyst. This allows histidine to accept a proton from NAD, which also draws a proton Thr 48. As a result of the proton transfer, the Thr is prepared to accept a proton from the alcohol substrate. While Thr accepts the proton, there is also a hydride transfer to NAD. The whole process can be summarized as the oxidation of an alcohol to an aldehyde in concert with the transfer of a hydride to NAD.^[8]

The Mechanism for alcohol dehydrogenase follows an random bisubstrate mechanism.^[9] In the mechanism, the NAD+ and alcohol bind to the enzyme, so that the enzyme is now attached to the two subtrates. While attached, the hydrogen is formally transferred from the alcohol to NAD, resulting in the products NADH and a ketone or aldehyde. The two products are then released, and the enzyme has catalyzed the reaction.

Kinetics

The alcohol dehydrogenase catalyzed aldehyde-NADH reaction show kinetics consistent with a random-order mechanism, and the rate-limiting step is the dissociation of the product enzyme-NAD+ complex. ^[10] Alcohol dehydrogenase is more effective for smaller alcohol substrates, and it becomes less effective as substrate size increases. It is also more effective for primary than secondary alcohols.^[11] In a study where ADH was immobilized in tresyl-chloride-activate agarose, it was shown that the Michaelis-Menten model could not take into consideration all the constraints induced by the immobilization on the enzyme properties but that the Theorell-Chance model was more appropriate.^[12]

Regulation

Substrate size is a regulator, where larger substrates inhibit alcohol dehydrogenase. Further, alcohol dehydrogenase is somewhat inhibited if the substrate is a secondary alcohol, as opposed to a primary alcohol. ^[13] Pyrazoles have also been shown to be inhibitors of ADH. ^[14] Other inhibitors include heavy metals, thiourea, purine and pyrimidine derivatives, and both chloroethanol and flouroethanol. ^[15] Activators include sulfhydryl activating reagents, mercaptoethanol, dithiothreitol, and cysteine.^[16]

Tetrameric alcohol dehydrogenases

spinqualitylabelsall models PDB ID 3fsr Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image The NADP+-dependent alcohol dehydrogenases from the thermophile Thermoanaerobacter brockii (TbADH), the mesophilic bacterium Clostridium beijerinckii (CbADH), and the protozoan parasite Entamoeba histolytica (EhADH1) are [1] (monomers are colored in different colors) secondary alcohol dehydrogenases. Each of these alcohol dehydrogenases consists of two domains: the (residues 154−294 for TbADH) and the (residues 1−153 and 295−351 for TbADH; contains Zn2+ at the active site) separated by a deep cleft. Although, all these three ADHs revealed a high degree of sequence conservation (62-75% identity), them significantly differ in thermostability. The cofactor-binding domains (residues 153−295) of TbADH, CbADH, and EhADH1 were mutually and 3 corresponding chimeras were constructed. The cofactor-binding domain of thermophilic TbADH was replaced with the cofactor-binding domain of its mesophilic counterpart CbADH (chimera Χ21(TCT), 3fsr). This domain replacement significantly destabilized the parent thermophilic enzyme (ΔT1/2 = −18 °C). But the reverse exchange in CbADH (chimera Χ22(CTC), 3fpl), had little effect on the thermal stability of the parent mesophilic protein. The exchange of the cofactor-binding domain of TbADH with the homologous domain of EhADH1 (chimera Χ23(TET), 3fpc) substantially reduced the thermal stability of the thermophilic ADH (ΔT1/2 = −51 °C) and interfered the oligomerization of the enzyme. The double mutant of the chimera Χ21(TCT) (cofactor-binding domain of thermophilic TbADH replaced by that of mesophilic CbADH) Q165E/S254K-X21(TCT) (3ftn) was constructed by site-directed mutagenesis. In both TbADH and CbADH, Lys257 and Asp237 form an intrasubunit ion pair, in TbADH, Asp237 is also involved in an ion pair bridge with Arg304 of the adjacent monomer. In addition, Arg304 forms intersubunit salt bridge with Glu165 of the first monomer. Therefore, a involving Lys257, Asp237, and Glu165 of one monomer and Arg304 of the adjacent one is present in TbADH (the names of monomers are in brackets). However in mesophilic CbADH (and, therefore, in the chimera Χ21(TCT), 3fsr) the Gln is situated in position 165 (instead Glu of TbADH) and Met in position 304 (instead Arg of TbADH), so, such an ion pair network does not exist. In the double mutant Q165E/S254K-X21(TCT) reverse mutation Q165E reconstructs this network (as in parent thermophilic TbADH) that led to significant enhancement of the thermal stability of CbADH (ΔT1/260 min = 5.4 °C). Chimera X21(TCT) (3fsr) is colored magenta and the double mutant Q165E/S254K-X21(TCT) cyan (3ftn). In chimera X21(TCT), position 254 is occupied by Ser (due to sequence of exchanged domain). The replacement of Ser254 of CbADH with Lys significantly enhances the stability of the enzyme, due to the formation of . However, this replacing of Ser254 by Lys had a negligible effect on the thermal stability, in contrast to mutation Q165E mentioned above. The of overall Cα backbone of all these chimeras (rmsd 0.45-0.65 Å) with those of the parent enzymes, did not reveal significant structural changes. So, the differences in the thermal stability of the chimeras and the parent enzymes could be caused by relatively small specific changes located at the important points of the NADP+-dependent alcohol dehydrogenases. For example see Cα superposition for the X23(TET) chimera (red) (3fpc) and its parent ADHs (TbADH, colored blue (1ped), and EhADH1, colored lime (1y9a). The RMSDs of the TbADH−EhADH1, TbADH−Χ23(TET), and EhADH1−Χ23(TET) were 0.68, 0.56, and 0.48 Å, respectively. The 3D structure of CbADH with the substitution Q100P () was solved at 2.25 Å resolution (2b83). The of Gln100 with Pro did not cause significant structural changes in the protein structure. The residues of the wildtype protein are colored lime and the residues of the mutant one in cyan. Only 2 H-bonds were lost, one between Oε1 of Gln100 and the main chain N of Gly297, and the second between Nε2 of Gln100 and the main chain carbonyl O of Gly297. The mutation caused that an additional CH2 group (Cδ of Pro100) is surrounded by nonpolar residues: Pro88 (3.8 Å), Trp90 (3.5 Å), and Val95 (4 Å). These residues (P100, P88, W90, and V95) are situated on a protruding lobe of the protein. An additional 11 aliphatic and aromatic carbon atoms are situated within the distance of 6 Å from Cδ of Pro100 (two methyl groups of Val95; three carbon atoms of the Trp90 indole group; Cβ and Cγ methylene groups of Pro100; Cβ and Cγ of Gln101, and two carbons of the Phe99 phenyl ring). Ribbon diagram of the EhADH1 (2oui). Proline residues (ball representation) are colored orange (Pro275) (which is important for thermal stabilization) and cyan (Pro100). of the structures of the wild-type apo-EhADH1 (colored lime, 1y9a) and the apo D275P-EhADH1 mutant (colored orange) (2oui). Pro275 and Asp275 are labeled red. Residues within a distance of 4 Å from the mutation are shown (names of monomers are in brackets). Replacing with significantly enhanced the thermal stability of EhADH1: ΔT1/260min = +9.3°C, ΔT1/2CD = +10°C. The reverse mutation in the thermophilic (1ykf; colored magenta) - substitution of wt TbADH Pro275 with (2nvb; colored cyan) reduced the thermal stability of the enzyme: ΔT1/260min = -13.8°C, ΔT1/2CD = -18.8°C. Nitrogen and oxygen atoms are colored in CPK colors. Pro275 and Asp275 are labeled red (names of monomers are in brackets). These findings indicate that a single proline mutation is responsible for the significant differences in the thermal stability of ADHs, and show the importance of prolines in the protein stability. It was also shown that substitution by proline at the important positions could significantly stabilize the protein.[17][18][19]

Additional Resources

For additional information, see: Carbohydrate Metabolism

3D Structures of Alcohol dehydrogenase

Update January 2013

ADH I

3jv7 – RrADH I – Rhodococcus rubber
2vna - hADH I catalytic domain - human
2hcy – yADH I – yeast
4eex – LlADH I – Lactococcus lactis
4eez – LlADH I (mutant)

ADH I binary complex

1u3t – hADH I α chain + inhibitor
1hsz, 1hdz, 3hud - hADH I β chain + NAD
1u3w - hADH I γ chain + inhibitor
1ht0 - hADH I γ chain (mutant) + NAD

ADH I ternary complex

2xaa – RrADH I + NAD + alcohol
3fx4 – pADH I + NADP + inhibitor – pig
2w98, 2w4q – hADH I catalytic domain + NADP + inhibitor
1hso - hADH I α chain + NAD + pyrazole derivative
1hdx - hADH I β chain + NAD + alcohol
1u3u, 1u3v - hADH I β chain + inhibitor
1deh, 1hdy - hADH I β chain + NAD + pyrazole derivative
1htb - hADH I β3 chain + NAD + pyrazole derivative

ADH II

3owo – ZmADH II iron-dependent – Zymomonas mobilis

ADH II binary complex

3ox4 - ZmADH II iron-dependent + NAD
3cos - hADH II + NAD + Zn
1e3e – mADH II + NADH – mouse
1e3l - mADH II (mutant) + NADH
1e3i - mADH II + NADH + inhibitor

ADH III

1m6h, 1m6w, 1teh - hADH III χ chain
2fze - hADH III χ chain + ADP-ribose
2fzw - hADH III χ chain + NAD
1mc5 – hADH III χ chain + glutathione + NADH
1ma0 - hADH III χ chain + dodecanoic acid + NAD
3qj5 - hADH III χ chain + inhibitor + NAD
4dl9, 4dlb – tADH III + NAD – tomato
4dla – tADH III

ADH IV

1ye3, 8adh, 5adh - hoADH IV e chain – horse
1qlj - hoADH IV e chain (mutant)
3iv7 – ADH IV – Corynebacterium glutamicum

ADH IV binary complex

2jhf, 2jhg, 1het, 1heu, 1hf3, 1ee2, 2oxi, 2ohx, 6adh - hoADH IV e chain + NAD
1adb, 1adc, 1adf, 1adg, 7adh - hoADH IV e chain + NAD derivative
1mgo, 1ju9, 1qlh, 1a72 - hoADH IV e chain (mutant) + NAD
1d1s, 1agn – hADH IV σ chain + NAD
1d1t - hADH IV σ chain (mutant) + NAD

ADH IV ternary complex

3oq6, 1qv6, 1qv7, 1a71, 1axe, 1axg – hoADH IV e chain (mutant) + NAD + alcohol
4dwv, 4dxh - hoADH IV e chain + NAD + alcohol
1p1r, 1ldy, 1lde - hoADH IV e chain + NADH + formamide derivative
1n92 - hoADH IV e chain + NAD + pyrazole derivative
1bto, 3bto - hoADH IV e chain + NADH + butylthiolane derivative
1n8k - hoADH IV e chain (mutant) + NAD + pyrazole
1mg0, 1hld - hoADH IV e chain + NAD + alcohol

ADH

1a4u – SlADH – Scaptodrosophila lebanonensis
3my7 – ADH ACDH domain – Vibrio parahaemolyticus
3meq – ADH – Brucella suis
3l4p – ADH – Desulfovibrio gigas
1jvb - SsADH – Sulfolobus solfataricus
3i4c, 1nto, 1nvg – SsADH (mutant)
3goh – ADH – Shewanella oneidensis
3gaz – ADH residues 2-334 – Novosphingobium aromaticivorans
2eih – ADH – Thermus thermophilus
1rjw – GsADH – Geobacillus stearothermophilus
1vj0, 1vhd – TmADH -Thermotoga maritima
2eer – ADH – Sulfolobus tokodaii
3uog – ADH – Sinorhizobium meliloti

ADH binary complex

3l77, 3tn7 – ADH short-chain + NADP – Thermococcus sibiricus
1h2b – ADH + NAD – Aeropyrum pernix
1f8f – Benzyl-ADH + NAD – Acinetobacter calcoaceticus
1o2d - TmADH + NADP
1b16, 1b14, 1b15 - SlADH + NAD derivative
1cdo – ADH + NAD - cod
1rhc – ADH F420-dependent +F420-acetone – Methanoculleus thermophilus
1agn – hADH (sigma) +NAD
3pii – GsADH + butyramide
3rj5, 3rj9 – SlADH (mutant) + NAD
3s1l – ADH + Zn – Ralstonia eutropha

ADH ternary complex

1mg5 – ADH + NADH + acetate – Drosophila melanogaster
1r37 – SsADH + NAD + alcohol
1sby – SlADH + NAD + alcohol
1b2l - SlADH + NAD + cyclohexanone
1llu - ADH + NAD + alcohol – Pseudomonas aeruginosa
3cv7 – pADH + NAD + NAP
3rf7 – SoADH + NAD + Fe + Ni

NADP-dependent ADH

1ped - CbADH – Clostridium beijerinckii
2b83, 1jqb – CbADH (mutant)
2nvb - TbADH (mutant) – Thermoanaerobacter brockii
3ftn, 3fpc, 3fpl, 3fsr – ADH chimera
1y9a - EhADH – Entamoeba histolytica
2oui – EhADH (mutant)
1p0c – RpADH8 – Rana perezi
4gac - mADH

NADP-dependent ADH binary complex

1kev – CbADH + NADPH
1bxz – CbADH catalytic domain + alcohol
1ykf – TbADH + NADP
3h4g – pADH + NADP
1p0f – RpADH + NADP

R-specific ADH

1nxq - LbRADH – Lactobacillus brevis
1zk2, 1zk3 - LbRADH (mutant)
1zjy, 1zjz, 1zk0, 1zk1 – LbRADH (mutant) + NADH + alcohol
1zk4 - LbRADH (mutant) + NADH + acetophenone

Specific alcohol ADH

2cf5, 2cf6 – Cinnamyl-ADH – Arabidopsis thaliana
1piw, 1q1n, 1ps0 – Cinnamyl-yADH
3two - Cinnamyl-ADH + NADP – Helicobacter pylori
1m2w – Mannitol-ADH – Pseudomonas fluorescens
1w6s – Methanol-ADH – Methylobacterium extorquens
1yqx – Sinapyl-aADH II – aspen
1yqd – Sinapyl-aADH II + NADP
1bdb – Biphenyl dihydrodiol-ADH + NAD - Pseudomonas

Quinohemoprotein ADH

1kv9, 1yiq – PpQADH II + PQQ + heme – Pseudomonas putida
1kb0 - QADH I + PQQ + heme – Comamonas testosteroni

Hydroxyacyl-CoA dehydrogenase

Short chain HADH

1so8 – hSHCDH II – human
3rqs - hSHCDH
1f14 - hSHCDH (mutant)

Short chain HADH binary complex

1f12 - hSHCDH (mutant) + hydroxybutyryl-CoA
1f17, 1lsj, 1lso - hSHCDH (mutant) + NAD
1zbq - hSHCDH IV + NAD
1e3s - rSHCDH + NAD – rat

Short chain HADH ternary complex

1u7t - hSHCDH II + inhibitor + NAD
1f0y - hSHCDH + acetoacetyl-CoA + NAD
1il0, 1m75, 1m76 - hSHCDH (mutant) + acetoacetyl-CoA + NAD
1e3w - rSHCDH + 3-keto-butyrate + NAD
1e6w - rSHCDH + estradiol + NAD

Unspecified HADH

1uay - HADH II – Thermus thermophilus
1zej, 3ctv - HADH – Archaeoglobus fulgidus
1zcj - rHADH
2x58 - rHADH + CoA
2et6 – HADH (mutant) – Candida tropicalis

References

1. ↑ Voet, et. al. Fundamentals of Biochemistry: 3rd Edition. Hoboken: Wiley & Sons, Inc, 2008.
2. ↑ Protein: Alcohol Dehydrogenase. The College of Saint Benedict and Saint John's University. 1 March 2010 < http://www.users.csbsju.edu/~hjakubow/classes/rasmolchime/99ch331proj/alcoholdehydro/index.htm>
3. ↑ Protein: Alcohol Dehydrogenase. The College of Saint Benedict and Saint John's University. 1 March 2010 < http://www.users.csbsju.edu/~hjakubow/classes/rasmolchime/99ch331proj/alcoholdehydro/index.htm>
4. ↑ Protein: Alcohol Dehydrogenase. The College of Saint Benedict and Saint John's University. 1 March 2010 < http://www.users.csbsju.edu/~hjakubow/classes/rasmolchime/99ch331proj/alcoholdehydro/index.htm>
5. ↑ Protein: Alcohol dehydrogenase from Human (Homo sapiens), different isozymes. SCOP. 2009. 1 March 2010 < http://scop.berkeley.edu/data/scop.b.d.c.b.b.c.html>
6. ↑ Protein: Alcohol Dehydrogenase. The College of Saint Benedict and Saint John's University. 1 March 2010 < http://www.users.csbsju.edu/~hjakubow/classes/rasmolchime/99ch331proj/alcoholdehydro/index.htm>
7. ↑ Voet, et. al. Fundamentals of Biochemistry: 3rd Edition. Hoboken: Wiley & Sons, Inc, 2008.
8. ↑ Protein: Alcohol Dehydrogenase. The College of Saint Benedict and Saint John's University. 1 March 2010 < http://www.users.csbsju.edu/~hjakubow/classes/rasmolchime/99ch331proj/alcoholdehydro/index.htm>
9. ↑ Voet, et. al. Fundamentals of Biochemistry: 3rd Edition. Hoboken: Wiley & Sons, Inc, 2008.
10. ↑ Dickinson FM, Monger GP. A study of the kinetics and mechanism of yeast alcohol dehydrogenase with a variety of substrates. Biochem J. 1973 Feb;131(2):261-70. PMID:4352908
11. ↑ Dickinson FM, Monger GP. A study of the kinetics and mechanism of yeast alcohol dehydrogenase with a variety of substrates. Biochem J. 1973 Feb;131(2):261-70. PMID:4352908
12. ↑ Bille V, Remacle J. Simple-kinetic descriptions of alcohol dehydrogenase after immobilization on tresyl-chloride-activated agarose. Eur J Biochem. 1986 Oct 15;160(2):343-8. PMID:3769934
13. ↑ Dickinson FM, Monger GP. A study of the kinetics and mechanism of yeast alcohol dehydrogenase with a variety of substrates. Biochem J. 1973 Feb;131(2):261-70. PMID:4352908
14. ↑ Blomstrand R, Ostling-Wintzell H, Lof A, McMartin K, Tolf BR, Hedstrom KG. Pyrazoles as inhibitors of alcohol oxidation and as important tools in alcohol research: an approach to therapy against methanol poisoning. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3499-503. PMID:115004
15. ↑ Alcohol Dehydrogenase. Worthington Biochemical Corporation . 31 March 2010 < http://http://www.worthington-biochem.com/ADH/default.html>
16. ↑ Alcohol Dehydrogenase.Worthington Biochemical Corporation . 31 March 2010 < http://http://www.worthington-biochem.com/ADH/default.html>
17. ↑ Goihberg E, Dym O, Tel-Or S, Levin I, Peretz M, Burstein Y. A single proline substitution is critical for the thermostabilization of Clostridium beijerinckii alcohol dehydrogenase. Proteins. 2007 Jan 1;66(1):196-204. PMID:17063493 doi:10.1002/prot.21170
18. ↑ Goihberg E, Dym O, Tel-Or S, Shimon L, Frolow F, Peretz M, Burstein Y. Thermal stabilization of the protozoan Entamoeba histolytica alcohol dehydrogenase by a single proline substitution. Proteins. 2008 Feb 7;. PMID:18260103 doi:10.1002/prot.21946
19. ↑ Goihberg E, Peretz M, Tel-Or S, Dym O, Shimon L, Frolow F, Burstein Y. Biochemical and Structural Properties of Chimeras Constructed by Exchange of Cofactor-Binding Domains in Alcohol Dehydrogenases from Thermophilic and Mesophilic Microorganisms. Biochemistry. 2010 Feb 9. PMID:20102159 doi:10.1021/bi901730x