Journal Issue - Volume 4 Issue 10 (October 1995)
Structural analysis of zinc substitutions in the active site of thermolysin
- Debra R. Holland, Andrew C. Hausrath, Doug Juers, Brian W. Matthews
- Published in Wiley Interscience on Dec 31, 2008
- DOI: 10.1002/pro.5560041001 (p 1955-1965)
Abstract Native thermolysin binds a single catalytically essential zinc ion that is tetrahedrally coordinated by three protein ligands and a water molecule. During catalysis the zinc ligation is thought to change from fourfold to fivefold. Substitution of the active‐site zinc with Cd2+, Mn2+, Fe2+, and Co2+ alters the catalytic activity (Holmquist B, Vallee BL, 1974, J Biol Chem 249:4601–4607). Excess zinc inhibits the enzyme. To investigate...
Stromelysin‐1: Three‐dimensional structure of the inhibited catalytic domain and of the C‐truncated proenzyme
- Joseph W. Becker, Alice I. Marcy, Laura L. Rokosz, Melinda G. Axel, Jonathan J. Burbaum, Paula M.D. Fitzgerald, Patricia M. Cameron, Craig K. Esser, William K. Hagmann, Jeffrey D. Hermes, James P. Springer
- Published in Wiley Interscience on Dec 31, 2008
- DOI: 10.1002/pro.5560041002 (p 1966-1976)
Abstract The proteolytic enzyme stromelysin‐1 is a member of the family of matrix metalloproteinases and is believed to play a role in pathological conditions such as arthritis and tumor invasion. Stromelysin‐1 is synthesized as a proenzyme that is activated by removal of an N‐terminal prodomain. The active enzyme contains a catalytic domain and a C‐terminal hemopexin domain believed to participate in macromolecular substrate...
Structural similarity between the pleckstrin homology domain and verotoxin: The problem of measuring and evaluating structural similarity
- C.A. Orengo, M.B. Swindells, A.D. Michie, M.J. Zvelebil, P.C. Driscoll, M.D. Waterfield, J.M. Thornton
- Published in Wiley Interscience on Dec 31, 2008
- DOI: 10.1002/pro.5560041003 (p 1977-1983)
Abstract An unexpected structural similarity is described between the pleckstrin homology (PH) domain and verotoxin. This similarity has escaped detection primarily due to the differences in topology that exist between the two proteins. By comparing this result with two previously reported similarities for the PH domain, one with the lipocalins and another with the FK506 binding protein, we discuss the problems of measuring and...
Water molecules participate in proteinase‐inhibitor interactions: Crystal structures of Leu Streptomyces griseus proteinase B
- Kui Huang, Michael N.G. James, Wuyuan Lu, Michael Laskowski, Stephen Anderson
- Published in Wiley Interscience on Dec 31, 2008
- DOI: 10.1002/pro.5560041004 (p 1985-1997)
Abstract Crystal structures of the complexes of Streptomyces griseus proteinase B (SGPB) with three P1 variants of turkey ovomucoid inhibitor third domain (OMTKY3), Leu18, Ala18, and Gly18, have been determined and refined to high resolution. Comparisons among these structures and of each with native, uncomplexed SGPB reveal that each complex features a unique solvent structure in the S1 binding pocket. The number and relative positions of water molecules...
Crystal structure of thioltransferase at 2.2 Å resolution
- Suresh K. Katti, Arthur H. Robbins, Yanfeng Yang, William W. Wells
- Published in Wiley Interscience on Dec 31, 2008
- DOI: 10.1002/pro.5560041005 (p 1998-2005)
Abstract We report here the first three‐dimensional structure of a mammalian thioltransferase as determined by single crystal X‐ray crystallography at 2.2 Å resolution. The protein is known for its thiol‐redox properties and dehydroascorbate reductase activity. Recombinant pig liver thioltransferase expressed in Escherichia coli was crystallized in its oxidized form by vapor diffusion technique. The structure was determined by multiple...
De novo design of the hydrophobic cores of proteins
- John R. Desjarlais, Tracy M. Handel
- Published in Wiley Interscience on Dec 31, 2008
- DOI: 10.1002/pro.5560041006 (p 2006-2018)
Abstract We have developed and experimentally tested a novel computational approach for the de novo design of hydrophobic cores. A pair of computer programs has been written, the first of which creates a “custom” rotamer library for potential hydrophobic residues, based on the backbone structure of the protein of interest. The second program uses a genetic algorithm to globally optimize for a low energy core sequence and structure,...
Prediction of polyelectrolyte polypeptide structures using Monte Carlo conformational search methods with implicit solvation modeling
- John Spencer Evans, Sunney I. Chan, William A. Goddard
- Published in Wiley Interscience on Dec 31, 2008
- DOI: 10.1002/pro.5560041007 (p 2019-2031)
Abstract Many interesting proteins possess defined sequence stretches containing negatively charged amino acids. At present, experimental methods (X‐ray crystallography, NMR) have failed to provide structural data for many of these sequence domains. We have applied the dihedral probability grid‐Monte Carlo (DPG‐MC) conformational search algorithm to a series of N‐ and C‐capped polyelectrolyte peptides, (Glu)20, (Asp)20. (PSer)20,...
Binary patterning of polar and nonpolar amino acids in the sequences and structures of native proteins
- Michael W. West, Michael H. Hecht
- Published in Wiley Interscience on Dec 31, 2008
- DOI: 10.1002/pro.5560041008 (p 2032-2039)
Abstract Protein sequences can be represented as binary patterns of polar (○) and nonpolar (•) amino acids. These binary sequence patterns are categorized into two classes: Class A patterns match the structural repeat of an idealized amphiphilic α‐helix (3.6 residues per turn), and class B patterns match the structural repeat of an idealized amphiphilic β‐strand (2 residues per turn). The difference between these two classes of...
Posttranslational modifications of bovine osteopontin: Identification of twenty‐eight phosphorylation and three O ‐glycosylation sites
- Esben S. Sørensen, Torben E. Petersen, Peter Højrup
- Published in Wiley Interscience on Dec 31, 2008
- DOI: 10.1002/pro.5560041009 (p 2040-2049)
Abstract Osteopontin (OPN) is a multiphosphorylated glycoprotein found in bone and other normal and malignant tissues, as well as in the physiological fluids urine and milk. The present study demonstrates that bovine milk osteopontin is phosphorylated at 27 serine residues and 1 threonine residue. Phosphoamino acids were identified by a combination of amino acid analysis, sequence analysis of S‐ethylcysteine‐derivatized...
Thermal stability determinants of chicken egg‐white lysozyme core mutants: Hydrophobicity, packing volume, and conserved buried water molecules
- Phoebe Shih, Jack F. Kirsch, Debra R. Holland
- Published in Wiley Interscience on Dec 31, 2008
- DOI: 10.1002/pro.5560041010 (p 2050-2062)
Abstract A series of 24 mutants was made in the buried core of chicken lysozyme at positions 40, 55, and 91. The midpoint temperature of thermal denaturation transition (Tm) values of these core constructs range from 60.9 to 77.3 °C, extending an earlier, more limited investigation on thermostability. The Tm values of variants containing conservative replacements for the wild type (WT) (Thr 40‐Ile 55‐Ser 91) triplet are linearly ...
Design and structural analysis of an engineered thermostable chicken lysozyme
- Phoebe Shih, Jack F. Kirsch
- Published in Wiley Interscience on Dec 31, 2008
- DOI: 10.1002/pro.5560041011 (p 2063-2072)
Abstract A hyperstable (hs) variant of chicken egg‐white lysozyme with enhanced thermal (ΔTm ≈︁ +10.5 °C) and chemical (ΔCm for guanidine hydrochloride denaturation = +1.3 M) stabilities relative to wild‐type (WT) was constructed by combining several individual stabilizing substitutions. The free energy difference between the native and denatured states of the hs variant is 3.1 (GdnHCl, 25 °C) to 4.0 (differential scanning calorimetry, 74 °C)...
Destabilizing loop swaps in the CDRs of an immunoglobulin V L domain
- Larry R. Helms, Ronald Wetzel
- Published in Wiley Interscience on Dec 31, 2008
- DOI: 10.1002/pro.5560041012 (p 2073-2081)
Abstract It is generally believed that loop regions in globular proteins, and particularly hypervariable loops in immunoglobulins, can accommodate a wide variety of sequence changes without jeopardizing protein structure or stability. We show here, however, that novel sequences introduced within complementarity determining regions (CDRs) 1 and 3 of the immunoglobulin variable domain REI VL can significantly diminish the stability of...
Identification of iron ligands in tyrosine hydroxylase by mutagenesis of conserved histidinyl residues
- S. Colette Daubner, Joel I. Ehrlich, Andrew J. Ramsey, Paul F. Fitzpatrick
- Published in Wiley Interscience on Dec 31, 2008
- DOI: 10.1002/pro.5560041013 (p 2082-2086)
Abstract Tyrosine hydroxylase catalyzes the hydroxylation of tyrosine and other aromatic amino acids using a tetrahydropterin as the reducing substrate. The enzyme is a homotetramer; each monomer contains a single nonheme iron atom. Five histidine residues are conserved in all tyrosine hydroxylases that have been sequenced to date and in the related eukaryotic enzymes phenylalanine and tryptophan hydroxylase. Because histidine has...
Atomic solvation parameters in the analysis of protein‐protein docking results
- Maxwell D. Cummings, Randy J. Read, Trevor N. Hart
- Published in Wiley Interscience on Dec 31, 2008
- DOI: 10.1002/pro.5560041014 (p 2087-2099)
Abstract Several sets of amino acid surface areas and transfer free energies were used to derive a total of nine sets of atomic solvation parameters (ASPs). We tested the accuracy of each of these sets of parameters in predicting the experimentally determined transfer free energies of the amino acid derivatives from which the parameters were derived. In all cases, the calculated and experimental values correlated well. We then chose...
Characterization of the isolated cAMP‐binding B domain of cAMP‐dependent protein kinase
- John B. Shabb, Mark A. Kapphahn, Wallace M. Muhonen, Celeste E. Poteet, Nancy E. Baker, Jackie D. Corbin
- Published in Wiley Interscience on Dec 31, 2008
- DOI: 10.1002/pro.5560041015 (p 2100-2106)
Abstract A 14.4‐kDa cAMP‐binding fragment was generated during bacterial expression and purification of recombinant bovine cAMP‐dependent protein kinase type Iα regulatory subunit (RIα). The full‐length RIα from which the fragment was derived contained a point mutation allowing its B domain to bind both cAMP and cGMP with high affinity while leaving its A domain highly cAMP selective. The NH2 terminus of the fragment was Ser‐252,...




