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Biographical Memoirs Volume 66 (1995) / Chapter Skim
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Myron Lee Bender
Pages 2-23

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From page 3...
... Later, he anct KoshIanct working inclepenclently invented a chemical procedure to convert the single serine residue in the protease subtilisin to a cysteine ancI thereby tested the importance of that single change in enzyme structure 3
From page 4...
... He made numerous other contributions to mechanistic organic chemistry and mechanistic enzymology and trained an influential group of bioorganic chemists. He was honored for his elegant science, notably by election to the National Academy of Sciences, and was active and inventive throughout his life.
From page 5...
... He carried out the hydrolysis of e tiny} benzoate and other esters marked with i80 in the carbonyl oxygen atom and shower! that the remaining starting material lost label as the reaction progressed.)
From page 6...
... The project solved an important problem and brought Bender instant recognition from the community of physical-organic chemists. He subsequently enlarged the research in this area.24
From page 7...
... have proved of great importance in the development of physical-organic chemistry, while one must note that some of the later works has not gone entirely unchallenged.6 The data, both from Bender's laboratory and from that of his critics, show that the exchange of isotopic oxygen in many cases accompanies the alkaline hydrolysis of esters and it is reasonable that, in some instances, the ratios of rate constants in the scheme above are such as to obscure that exchange. Since the exchange does occur in a number of examples it offers firm evidence supporting a tetrahedral intermediate in ester hydrolysis.
From page 8...
... Bender's spectroscopic demonstrations that a cinnamate ester of chymotrypsin is formed during the enzymic hydrolysis of ~nitrophenyl cinnamate fits with, and strongly reinforces, the earlier work of Balls and Hartley. Of course, as one examines the Balls-Hartley pathway more closely, one realizes that each step in the formation or decomposition of an ester or amide presumably proceeds through a i
From page 9...
... MYRON LEE BENDER Subs&¢ate Ser 195 ,R O=C —CH2-O ~ ~ R-N-H H N—CH His 57 HC ~ ~ N—C H I ~ cH2 O \ 1 C=0 Apyl-enzyme O;'C—R' —CH2—O His 57 HC H O' H N—CH ~ ., N C H I , CH2 O \ Asp 102 C=0 Tetrahedral intermediate Acyl-enzyme C —CH2-O R-N-H —CH2—O H N CH 11 HC H O* c'O N—C Tetrahedral intermediate CH~: C —CH2—O ~o—H H N—CH ,, HC\ O*
From page 10...
... comes from the work of Shaw and his coworkers,~4 who showed the Ntosy~phenylalany} chIoromethyl ketone reacts stoichiometrically with a histidine residue of the enzyme. The histicline serves to pull a proton from the hydroxyl group of the essential serine residue, and thus makes it much more nucleophilic.
From page 11...
... With respect to the serine proteases perhaps the most important example of mechanistic enzymology—X-ray crystallography largely confirmed what had already been established by protein chemistry and enzyme kinetics. The kinetic analysis to the two-step mechanism led to the equation shown below: E + S,gES k_i ~ES' +P1 ~E+P2 Here PI is ammonia, an alcohol, or a peptide.
From page 12...
... each substrate will react at a different maximal velocity and the Michaelis constant will correctly represent the binding of substrate to enzyme. Bender en cl his coworkers demonstrated that the abunclant data for the hydrolysis of various substrates by chymo
From page 13...
... Bender had previously provided spectroscopic evidence for the formation of an acetylated enzyme with unnatural substrates. Now Kezcly and Bender22 answered some of the last objections to this mechanism when they demonstrated spectroscopically the formation of an intermediate with natural substrates and showed that the decomposition of the acyI-enzyme intermediate occurred at a rate consistent with that calculated by the kinetic scheme of Bender and Zerner.
From page 14...
... Polgar and Bender converted subtilisin into thiosubtilisin by chemical transformation of the essential serine residue to a cysteine. The same chemistry was independently achieved by Neet and Koslancl.2i Today this type of transformation is accomplished almost routinely through synthesis and expression of appropriately modified nucleic acids.
From page 15...
... .24~27 Similarly, he worked with bicyclic systems, where the molecular geometry placed catalytic sites close to ester linkages, much as they must be in the active site of serine esterases.28 In the structure shown in Figure 4, for example, Bender used an imiciazole residue to simulate the histidine in chymotrypsin, en cl a carboxylate residue, properly placed, to simulate the aspartate in chymotrypsin. Most models for esterases are active only in the hydrolysis of highly activated esters such as pnitropheny]
From page 16...
... In this case, contrary to most of our unclerstanding of the mechanism of action of the serine esterases, X-ray analysis preceded chemistry. The work on benzoate catalysis was carried out shortly before Bender's cleath and showed how active he was right up to the end of his life.
From page 17...
... In fact, our understanding of the mechanism of enzymic hydrolysis of esters and amides comes in large part from Bender's probing experiments and critical examinations of the resulting data. All of these accomplishments distinguish Myron Bender as a major contributor to the development of big-organic chemistry in our time.
From page 18...
... Kinetic evidence for the formation of acylenzyme intermediates in the a-chymotrypsin-catalyzed hydrolysis of specific substrates.
From page 19...
... Ester hydrolysis catalyzed by modified cyclodextrins. Bioorg.
From page 20...
... 81:4746. 1960 Mechanisms of catalysis of nucleophilic reactions of carboxylic acid derivatives.
From page 21...
... The application of insolubilized chymotrypsin to kinetic studies on the effect of aprotic dipolar organic solvents.
From page 22...
... Miniature organic models of enzymes. Accts.
From page 23...
... Komiyama. The Bioorganic Chemistry of Enzymatic Catalysis.


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