The Left-Handed Parallel Beta Helix

Enzymes containing the Left-Handed Parallel Beta Helix domain display imperfect tandem-repeated copies of a hexapeptide sequence characterized as [LIV]-[GAED]-X2-[STAV]-X and are termed 'hexapeptide repeat' enzymes. Because most of these enzymes are also Coenzyme A or acyl-Acyl Carrier Protein dependent acyltransferases, they are also termed'hexapeptide acyltransferases'. The hexapeptide sequence encodes a three-dimensional fold that approximates a left-handed triangular coil with sides composed of short parallel beta strands. We are currently studying several of these enzymes with the aim of identifying their catalytic mechanisms of action and the amino acid sequence rules that direct folding of this domain.

(UPPER LEFT) Single subunit ribbon diagram of UDP-GlcNAc O-Acyltransferase (LpxA) (Raetz, C.R.H. and Roderick, S.L. (1995). "A Left-Handed Parallel Beta Helix in the Structure of UDP-N-Acetylglucosamine Acyltransferase". Science 270, 997-1000). The loops that project from the beta helix disobey the 'hexapeptide repeat' sequence rule and therefore cannot be accomodated in the helical fold. These loops may be of catalytic importance.

(UPPER RIGHT) The Left-Handed Parallel Beta Helix domain of the THDP-N-Succinyltransferase Trimer (Beaman, T.W., Binder, D.A., Blanchard, J.S. and Roderick, S.L. (1997). "Three-Dimensional Structure of Tetrahydrodipicolinate N-Succinyltransferase". Biochemistry 36, 489-494). The conserved residues at the [LIV] position of the 'hexapeptide repeat' sequence stack on top of one another and can be seen projecting inward toward the lumen of each beta helix to form an ordered hydrophobic core. The apparent hole down the middle of each domain is not wide enough for solvent molecules to fit inside the helix.

(BELOW) The three faces of the Left-Handed Parallel Beta Helix domain. These faces are remarkably flat parallel beta sheets composed of very short beta strand segments. These segments are connected by tight turns. The pattern of interstrand hydrogen bonding between main chain amide and carbonyl groups is shown below.

The Left-Handed Parallel Beta Helix fold is one of several all parallel beta domain folds. The first of these folds was discovered by Jurnak, Yoder and co-workers in the structure of Pectate Lyase C. Other right-handed all parallel beta folds are found in the P22 Tailspike Protein, Pseudomonas aeruginosa Alkaline Protease and Pertactin. The Left-Handed Parallel Beta Helix fold is the only all parallel beta domain fold employing left-handed crossover connections between beta strands.

(BELOW) Single subunit ribbon diagrams of parallel beta domain proteins. (Left to Right) Pectate Lyase C (PelC), P22 Tailspike Protein (TSP), UDP-GlcNAc O-Acyltransferase (LpxA) and Pseudomonas aeruginosa Alkaline Protease (AlkP). PelC and AlkP are monomeric. TSP and LpxA are trimers.

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