PDBsum entry 1v1d

Hormone

PDB id

1v1d

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Contents

			Protein chain

					31 a.a. *

* Residue conservation analysis

PDB id:

1v1d

Links
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Name:

Hormone

Title:

Nucleophilic and general acid catalysis at physiological ph by a designed miniature esterase

Structure:

Pancreatic hormone. Chain: a. Fragment: pancreatic polypeptide residues 30-60. Synonym: pancreatic polypeptide, pp. Engineered: yes. Mutation: yes

Source:

Synthetic: yes. Bos taurus. Bovine. Organism_taxid: 9913

NMR struc:

20 models

Authors:

A.Nicoll,R.K.Allemann

Key ref:

A.J.Nicoll and R.K.Allemann (2004). Nucleophilic and general acid catalysis at physiological pH by a designed miniature esterase. Org Biomol Chem, 2, 2175-2180. PubMed id: 15280952

Date:

14-Apr-04

Release date:

14-Apr-05

PROCHECK

	Headers

	References

Protein chain

P01302 (PAHO_BOVIN) - Pancreatic polypeptide prohormone from Bos taurus

Seq: Struc:					131 a.a. 31 a.a.*

Key:

PfamA domain

Secondary structure

* PDB and UniProt seqs differ at 3 residue positions (black crosses)



		Enzyme reactions

Enzyme class:

E.C.?

[IntEnz] [ExPASy] [KEGG] [BRENDA]

	Org Biomol Chem 2:2175-2180 (2004)
PubMed id: 15280952

Nucleophilic and general acid catalysis at physiological pH by a designed miniature esterase.
A.J.Nicoll, R.K.Allemann.

ABSTRACT

A 31-residue peptide (Art-Est) was designed to catalyse the hydrolysis of p-nitrophenyl esters through histidine catalysis on the solvent exposed face of the alpha-helix of bovine pancreatic polypeptide. NMR spectroscopy indicated that Art-Est adopted a stable 3-dimensional structure in solution. Art-Est was an efficient catalyst with second order rate constants of up to 0.050 M(-1) s(-1). The activity of Art-Est was a consequence of the increased nucleophilicity of His-22, which had a reduced pK(a) value of 5.5 as a consequence of its interaction with His-18 and the positively charged Arg-25 and Arg-26. Mass spectrometry and NMR spectroscopy confirmed that the Art-Est catalysed hydrolysis of p-nitrophenyl esters proceeded through an acyl-enzyme intermediate. A solvent kinetic isotope effect of 1.8 indicated that the transition state preceding the acyl intermediate was stabilised through interaction with the protonated side-chain of His-18 and indicated a reaction mechanism similar to that generally observed for natural esterases. The involvement in the reaction of two histidine residues with different pK(a) values led to a bell-shaped dependence of the reaction rate on the pH of the solution. The catalytic behaviour of Art-Est indicated that designed miniature enzymes can act in a transparent mechanism based fashion with enzyme-like behaviour through the interplay of several amino acid residues.

Literature references that cite this PDB file's key reference

PubMed id

Reference

19012293

L.Vial, and P.Dumy (2008).
Nanomolar heparin detection with an artificial enzyme.

Chembiochem, 9, 2950-2953.

17973491

J.H.Holtzman, K.Woronowicz, D.Golemi-Kotra, and A.Schepartz (2007).
Miniature protein ligands for EVH1 domains: interplay between affinity, specificity, and cell motility.

Biochemistry, 46, 13541-13553.

16547956

A.Hunding, F.Kepes, D.Lancet, A.Minsky, V.Norris, D.Raine, K.Sriram, and R.Root-Bernstein (2006).
Compositional complementarity and prebiotic ecology in the origin of life.

Bioessays, 28, 399-412.

16327890

A.J.Nicoll, C.J.Weston, C.Cureton, C.Ludwig, F.Dancea, N.Spencer, O.S.Smart, U.L.Günther, and R.K.Allemann (2005).
De novo design of a stable N-terminal helical foldamer.

Org Biomol Chem, 3, 4310-4315.

15995697

S.A.Benner, and A.M.Sismour (2005).
Synthetic biology.

Nat Rev Genet, 6, 533-543.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.