Exam 1 proteins

What are the four non-covalent forces stabilizing proteins?

Ionic interactions, hydrogen bonds, van der Waals forces, and the hydrophobic effect.

Which non-covalent interaction is strongest individually, and which dominates total protein stability?

A salt bridge is strongest individually; the hydrophobic effect dominates overall stability.

Why does the hydrophobic effect stabilize proteins?

Burying nonpolar groups releases ordered water, creating a favorable entropy change; nonpolar groups are not directly “attracted.”

What is the typical energy range given for a hydrogen bond?

About 2–10 kJ/mol per hydrogen bond.

What is the typical energy range given for a van der Waals interaction?

About 0.4–4 kJ/mol, with optimal separation around 3.5 Å.

How do statherin and acidic PRPs initially bind enamel?

Their anionic phosphoserine/carboxylate groups bind enamel-associated Ca²⁺ ionically.

What happens to pellicle formation if calcium is chelated?

It is abolished because the initial protein–mineral ionic interaction is disrupted.

What four substituents are attached to the α-carbon of a standard amino acid?

NH₃⁺, COO⁻, H, and the R group.

Which amino acid is achiral, and why?

Glycine, because its R group is H, giving the α-carbon two identical substituents.

How is L vs D assigned in the Fischer convention used here?

NH₂ on the left = L; NH₂ on the right = D; horizontal bonds project toward the viewer.

What stereoisomeric form do human proteins use?

L-amino acids.

Why are β-lactams selectively toxic to bacteria in the lecture’s framework?

Bacterial peptidoglycan contains D-alanine and D-glutamate; human proteins are built from L-amino acids and host enzymes are stereospecific.

What dental/forensic use is made of D-aspartate formation?

Slow racemization of L-aspartate to D-aspartate in long-lived dentin collagen can be used for age estimation.

Which amino acids are Group I: nonpolar aliphatic?

Gly, Ala, Val, Leu, Ile, Pro, Met.

Which amino acids are Group II: aromatic?

Phe, Tyr, Trp.

Which amino acids are Group III: polar uncharged?

Ser, Thr, Cys, Asn, Gln.

Which amino acids are Group IV: basic at pH 7.4?

Lys, Arg, His.

Which amino acids are Group V: acidic at pH 7.4?

Asp and Glu.

Which aromatic amino acids absorb at 280 nm?

Tyrosine and tryptophan.

Why is proline structurally unusual?

Its ring locks backbone φ and it lacks a backbone N–H, restricting rotation and favoring turns/helix disruption.

What important collagen modification involves proline?

Vitamin C-dependent hydroxylation of proline to 4-hydroxyproline.

What does cysteine’s thiol group allow?

Oxidation to a disulfide bond; important for stabilizing secreted proteins and cross-linking mucins.

How does cysteine contribute to oral disease biology in the guide?

It helps cross-link MUC5B, stabilizes secretory IgA, and acts as the catalytic nucleophile in gingipains.

What are the approximate 280-nm extinction coefficients given for Trp and Tyr?

Trp ≈ 5,500; Tyr ≈ 1,490.

Why is histidine especially important in oral biochemistry?

Its imidazole pKa ≈ 6.0, so its protonation changes across the oral pH range; it is important in buffering and histatin charge.

Which amino acids contribute to volatile sulfur compounds in halitosis?

Methionine and cysteine.

What are the nine essential amino acids in the course mnemonic?

Phe, Val, Thr, Trp, Ile, Met, His, Leu, Lys (PVT TIM HaLL).

Which amino acids are conditionally essential in the guide?

Arg, Cys, Gln, Gly, Pro, Tyr.

When can conditionally essential amino acids become dietarily required?

Prematurity, severe illness, burns, or liver disease.

When does tyrosine become essential?

In phenylketonuria, when phenylalanine cannot adequately serve as its precursor.

What oral findings can appear early in niacin deficiency from inadequate tryptophan?

Atrophic glossitis, stomatitis, and angular cheilitis.

What are oral consequences of protein–energy malnutrition noted in the guide?

Delayed wound healing and a blunted neutrophil response in the periodontium.

What is the rule for protonation vs deprotonation relative to pKa?

pH below pKa → protonated; pH above pKa → deprotonated.

What is the relationship between pH, pI, and protein charge?

At pH = pI, net charge is zero; at pH above pI, the molecule is generally more negative; at pH below pI, more positive.

Why is statherin anionic and able to bind enamel calcium?

Its pI ≈ 4.2, so at oral pH it carries net negative charge and can interact with mineral Ca²⁺.

Why is histatin 5 strongly attracted to microbial membranes?

Its high pI (~10) makes it cationic at oral pH, favoring binding to anionic microbial membranes.

What is the peptide bond chemically?

A condensation product between a carboxyl group and an amino group with loss of water.

Why is the peptide bond planar?

Resonance gives the C–N bond partial double-bond character (~40%), restricting rotation.

What fraction of peptide bonds are trans in the guide?

About 99.9%; cis is largely restricted to X–Pro bonds.

Which backbone angles can rotate freely around single bonds?

φ (N–Cα) and ψ (Cα–C).

Which amino acid is most conformationally restricted and which is most permissive?

Proline is most restricted; glycine is most permissive.

Why is glycine required at every third position in collagen?

Every third side chain points toward the crowded triple-helix axis; only glycine’s H fits there.

In what direction are peptide sequences written?

N-terminus → C-terminus.

Which groups contribute to peptide net charge in a simple charge calculation?

The free N-terminus, free C-terminus, and ionizable side chains (Asp, Glu, Lys, Arg, His, Cys, Tyr).

What is the net charge of Ser-Phe-Asp-Ala-Glu at pH 7.4?

−2: +1 N-terminus and −1 each from C-terminus, Asp, and Glu.

What is the net charge of Ser-Phe-Asp-Ala-Glu at pH 2.0 in the guide?

+1 because the carboxyl groups are protonated while the N-terminus remains positive.

What is histatin 5 and what is its key oral role?

A 24-residue, histidine-rich, strongly cationic peptide that is potently fungicidal against Candida albicans.

What are β-defensins and LL-37?

Cationic antimicrobial peptides associated with oral epithelium and neutrophils; LL-37 is the only human cathelicidin.

What do statherin and acidic PRPs do?

They bind hydroxyapatite and help keep saliva supersaturated with calcium phosphate.

What is glutathione’s sequence and unusual linkage?

γ-Glu-Cys-Gly; it contains an unusual γ-peptide bond that resists ordinary peptidases.

What do Substance P and CGRP do in the pulp?

They are released from pulpal sensory nerves and contribute to neurogenic inflammation in pulpitis.

What does SDS do in SDS-PAGE?

It denatures proteins and gives them a near-uniform negative charge so separation is based mainly on size.

What does a Western blot add to SDS-PAGE?

An antibody probe adds molecular identity/specificity while the gel provides apparent molecular weight.

What does chairside aMMP-8 indicate?

Active periodontal collagen breakdown in gingival crevicular fluid.

Why is aMMP-8 more dynamic than probing depth?

aMMP-8 reflects active collagen breakdown; probing depth is more of a historical structural measurement.

What are the one-letter and three-letter codes for alanine?

A; Ala.

What are the one-letter and three-letter codes for arginine?

R; Arg.

What are the one-letter and three-letter codes for asparagine?

N; Asn.

What are the one-letter and three-letter codes for aspartate?

D; Asp.

What are the one-letter and three-letter codes for cysteine?

C; Cys.

What are the one-letter and three-letter codes for glutamate?

E; Glu.

What are the one-letter and three-letter codes for glutamine?

Q; Gln.

What are the one-letter and three-letter codes for glycine?

G; Gly.

What are the one-letter and three-letter codes for histidine?

H; His.

What are the one-letter and three-letter codes for isoleucine?

I; Ile.

What are the one-letter and three-letter codes for leucine?

L; Leu.

What are the one-letter and three-letter codes for lysine?

K; Lys.

What are the one-letter and three-letter codes for methionine?

M; Met.

What are the one-letter and three-letter codes for phenylalanine?

F; Phe.

What are the one-letter and three-letter codes for proline?

P; Pro.

What are the one-letter and three-letter codes for serine?

S; Ser.

What are the one-letter and three-letter codes for threonine?

T; Thr.

What are the one-letter and three-letter codes for tryptophan?

W; Trp.

What are the one-letter and three-letter codes for tyrosine?

Y; Tyr.

What are the one-letter and three-letter codes for valine?

V; Val.

What is primary structure, and why is it clinically important?

Primary structure is the gene-encoded amino acid sequence written N → C. It determines all higher-order structure, so a single substitution can alter charge, stability, an active site, an interaction surface, or protease processing.

Why can a single amino acid substitution cause disease even if most of the protein sequence is normal?

A single substitution can change net charge, folding stability, an active site, an interaction surface, or create/destroy a protease cleavage site.

Why is a glycine substitution especially disruptive in collagen?

Collagen uses a (Gly–X–Y)n repeat. Glycine fits the crowded center of the triple helix; replacing it forces a larger side chain into the axis and creates a destabilizing bulge.

Why can a missense collagen variant be worse than a null allele?

Collagen is a trimer. A mutant chain can be incorporated into trimers and exert a dominant-negative effect, so roughly three-quarters of assembled molecules may be defective, whereas a null allele mainly reduces the amount of otherwise normal protein.

What is the difference between a polypeptide and a free amino acid?

A polypeptide is a chain of residues linked by peptide bonds; each residue has lost the elements of water during peptide-bond formation.

Which structural level is held together by covalent bonds?

Primary structure. The peptide bonds are covalent; higher-order organization depends mainly on noncovalent interactions plus disulfides where present.

How can a sequence substitution affect protein processing without changing the protein's overall fold?

Proteases recognize short stretches of sequence rather than overall shape, so a substitution can create or destroy a protease cleavage site.

Which proteases must process amelogenin for enamel to harden?

MMP-20 trims amelogenin during the secretory stage, and KLK4 clears the remaining matrix during maturation.

Which enzyme cleaves the procollagen N-propeptide?

ADAMTS2.

Why does ACE inhibition cause angioedema of the lip and tongue according to the study guide?

ACE normally inactivates bradykinin at Pro7–Phe8. ACE inhibition allows bradykinin to accumulate, promoting angioedema.

What stabilizes an α-helix?

Backbone hydrogen bonds within the same stretch of chain: the C=O of residue n hydrogen-bonds to the N–H of residue n+4.

How many residues occur per turn of an α-helix?

About 3.6 residues per turn.

Where do the R groups point in an α-helix?

Outward from the helix.

How are β-sheet hydrogen bonds arranged?

Between adjacent strands, which may be far apart in the primary sequence.

Why are antiparallel β-sheets generally more stable than parallel β-sheets?

Antiparallel strands form straighter, stronger backbone hydrogen bonds; parallel strands form skewed, weaker hydrogen bonds.

Which residues are listed as α-helix formers in this lecture?

Met, Ala, Arg, Lys, Leu, and Glu.

Which residues are listed as β-sheet formers?

Thr, Val, and Ile, especially the β-branched residues.

Why does proline break α-helices?

Proline lacks a backbone N–H donor and its ring constrains φ, disrupting the regular helical hydrogen-bond pattern.

Why does glycine break α-helices?

Glycine is extremely flexible, so fixing it into one helical conformation is unfavorable.

How is the collagen triple helix different from an α-helix?

Collagen consists of three extended polyproline-like helices wound together, with hydrogen bonds between chains rather than within one chain.

What is tertiary structure?

The complete three-dimensional fold of one polypeptide chain, bringing residues distant in sequence together in space.

What force contributes most to tertiary folding?

The hydrophobic effect is the main driver; hydrogen bonds and salt bridges help specify the fold, and disulfides can provide a covalent staple.

Why are disulfide bonds especially important in secreted proteins?

The extracellular environment is relatively oxidizing, whereas the cytosol is reducing. Secreted proteins can therefore use disulfides to stabilize their structures.

Name three oral examples that use disulfides.

Lysozyme, secretory IgA, and MUC5B.

What is a protein domain?

A portion of a protein that can fold independently and often carries a particular function.