Hydrogen bonds involving sulfur atoms in proteins

Gregoret, Lydia M.; Rader, Stephen D.; Fletterick, Robert J.; Cohen, Fred E.

doi:10.1002/prot.340090204

Cited by 239 publications

(225 citation statements)

References 19 publications

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“…Although sulfur is not as electronegative as oxygen, it would still be expected to make an excellent nucleophile for attack on the acetyl carbonyl carbon. The slightly longer sulfur-carbon bond pushes the sulfur atom into a position such that it can make potential hydrogen bonds with both His 158 and His 193 that are significantly longer than the corresponding oxygen hydrogen bonds (32 His 158 and the O␥ of serine would prevent the formation of a hydrogen bond to His 193 at the same time, thus the binding of cysteine is expected to be significantly tighter than that of serine, and this may increase the activation energy sufficiently to prevent catalysis. This difference in binding may account for some of the 4.4 kcal⅐mol Ϫ1 apparent difference in binding energies of serine and cysteine calculated by Hindson (16).…”

Section: Discussionmentioning

confidence: 99%

The Structure and Mechanism of Serine Acetyltransferase from Escherichia coli

Pye

Tingey

Robson

et al. 2004

Journal of Biological Chemistry

103

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Serine acetyltransferase (SAT) catalyzes the first step of cysteine synthesis in microorganisms and higher plants. Here we present the 2.2 Å crystal structure of SAT from Escherichia coli, which is a dimer of trimers, in complex with cysteine. The SAT monomer consists of an amino-terminal ␣-helical domain and a carboxyl-terminal left-handed ␤-helix. We identify His 158 and Asp 143as essential residues that form a catalytic triad with the substrate for acetyl transfer. This structure shows the mechanism by which cysteine inhibits SAT activity and thus controls its own synthesis. Cysteine is found to bind at the serine substrate site and not the acetyl-CoA site that had been reported previously. On the basis of the geometry around the cysteine binding site, we are able to suggest a mechanism for the O-acetylation of serine by SAT. We also compare the structure of SAT with other left-handed ␤-helical structures.Serine acetyltransferase (SAT) 1 participates in the dual-step process of sulfur assimilation of microorganisms (1-3) and higher plants (4, 5). First, SAT catalyzes the production of O-acetyl-L-serine from acetyl-CoA and L-serine, and then Oacetyl serine (thiol) lyase (OAS-TL) converts O-acetyl-L-serine into L-cysteine in the presence of sulfide. Kredich and co-workers (2, 6) reported that SAT (from Salmonella typhimurium) represents the rate-limiting component and is reversibly associated with ϳ5% of the total cellular OAS-TL to form the multi-enzyme complex referred to as "cysteine synthase." Cysteine constitutes the almost exclusive metabolic entrance for reduced sulfur into cell metabolism, where it is required for biosynthesis of essential compounds including methionine, several vitamins, and metal clusters (7). The production of cysteine is therefore of biotechnological interest for pharmacological processes and as a nutritional supplement for food and feed.SAT is known to be a member of the bacterial O-acetyltransferases subfamily of O-acyltransferases (8, 9), where amino acid sequence, tertiary structures, and mechanisms are known. The folding pattern that dominates the O-acetyltransferase family is the left-handed ␤-helix, which is recognized by a hexapeptide repeating signature in which residue i is aliphatic, i ϩ 1 is usually glycine, and i ϩ 4 is a small residue, thusStructures are triangular in crosssection and are formed by parallel ␤-strands folding into a helix with three strands per turn. The first of such proteins to be studied by x-ray crystallography was the lpxA gene product that was shown to be a trimeric protein with this left-handed ␤-helical fold (10). A folding pattern arises from a hexapeptide repeat, which occurs, albeit to varying degrees, in other members of the O-acyltransferase family. SAT has such hexapeptide repeats at its carboxyl-terminal region. The three clefts between the three subunits form the catalytic centers in which a histidine residue is essential for transfer of the acetyl or succinyl moiety from CoA to the second substrate. From the sequence alignment in Fig. 1...

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Section: Discussionmentioning

confidence: 99%

The Structure and Mechanism of Serine Acetyltransferase from Escherichia coli

Pye

Tingey

Robson

et al. 2004

Journal of Biological Chemistry

103

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“…Cohen and coworkers have surveyed the protein data bank and found that 72% of all reduced cysteine residues in proteins are involved in hydrogen bonding (Gregoret et al, 1991). Of these residues, 58% are involved in hydrogen bonding to carbonyl oxygens at position i-4 of an ␣-helix.…”

Section: Sulfhydryl Vibrational Modes: Hydrogen-bonding and Conformationmentioning

confidence: 99%

Structure of the Transmembrane Cysteine Residues in Phospholamban

Arkin

Adams

Brünger

et al. 1997

Journal of Membrane Biology

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Abstract. Phospholamban, a 52-residue membrane protein, associates to form a pentameric complex of five long ␣-helices traversing the sarcoplasmic reticulum membrane of cardiac muscle cells. The transmembrane domain of the protein is largely hydrophobic, with only three cysteine residues having polar side chains, yet it functions as a Ca 2+ -selective ion channel. In this report, infrared spectroscopy is used to probe the conformation of the three cysteine side chains and to establish whether the free S-H groups form intrahelical hydrogen bonds in the pentameric complex. Vibrational spectra of a transmembrane peptide were obtained which corresponded to the transmembrane domain of wild-type phospholamban and three peptides each containing a cysteine ⇒ alanine substitution. The observed S-H frequencies argue that each of the sulfhydryl groups is hydrogen-bonded to an i-4 backbone carbonyl oxygen. Electrostatic calculations on a model of phospholamban based on molecular dynamics and mutagenesis studies, show that the sulfhydryl groups may significantly contribute to the electrostatic potential field of the protein.

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“…Ecotin's secondary binding site for proteases buries little surface area and would probably be unstable in the absence of the primary interaction. (Gellman, 1991) as well as being a potential hyfound between ecotin Met 84-N (Pl) and trypsin Ser 214-0, and drogen bond acceptor (Gregoret et al, 1991). between ecotin Ser 82-N and 0 (P3) with trypsin Gly 216-0 and N, respectively.…”

Section: Figmentioning

confidence: 99%

Ecotin: Lessons on survival in a protease‐filled world

1995

Self Cite

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Ecotin, an Escherichia coli periplasmic protein of 142 amino acids, has been shown to be a potent inhibitor of a group of homologous serine proteases with widely differing substrate recognition. It is highly effective against a number of enzymes, including both pancreatic and neutrophil-derived elastases, chymotrypsin, trypsin, factor Xa, and kallikrein. Recent structural and functional studies on ecotin and its interactions with different serine proteases have clarified these initial observations and revealed the remarkable features of this protein in inhibiting a strikingly large subset of the chymotrypsin family of serine proteases. The structures of the ecotinserine protease complexes provide the first examples of protein-protein recognition where the concept of specificity of interactions needs to be reexamined. The binding sites show a fluidity of protein contacts derived from ecotin's innate flexibility in fitting itself to proteases while strongly interfering with their function.

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Hydrogen bonds involving sulfur atoms in proteins

Cited by 239 publications

References 19 publications

The Structure and Mechanism of Serine Acetyltransferase from Escherichia coli

The Structure and Mechanism of Serine Acetyltransferase from Escherichia coli

Structure of the Transmembrane Cysteine Residues in Phospholamban

Ecotin: Lessons on survival in a protease‐filled world

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